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Smoking Cessation Reduces Postoperative Complications: A Systematic Review and Meta-analysis

      Abstract

      Objective

      We aimed to review randomized trials and observational evidence to establish the effect of preoperative smoking cessation on postoperative complications and to determine if there is an optimal cessation period before surgery.

      Methods

      We conducted a systematic review of all randomized trials evaluating the effect of smoking cessation on postoperative complications and all observational studies evaluating the risk of complications among past smokers compared with current smokers. We searched independently, in duplicate, 10 electronic databases and the bibliographies of relevant reviews. We conducted a meta-analysis of randomized trials using a random effects model and performed a meta-regression to examine the impact of time, in weeks, on the magnitude of effect. For observational studies, we pooled proportions of past smokers in comparison with current smokers.

      Results

      We included 6 randomized trials and 15 observational studies. We pooled the 6 randomized trials and demonstrated a relative risk reduction of 41% (95% confidence interval [CI], 15-59, P = .01) for prevention of postoperative complications. We found that each week of cessation increases the magnitude of effect by 19%. Trials of at least 4 weeks' smoking cessation had a significantly larger treatment effect than shorter trials (P = .04). Observational studies demonstrated important effects of smoking cessation on decreasing total complications (relative risk [RR] 0.76, 95% CI, 0.69-0.84, P < .0001, I2 = 15%). This also was observed for reduced wound healing complications (RR 0.73, 95% CI, 0.61-0.87, P = .0006, I2 = 0%) and pulmonary complications (RR 0.81, 95% CI, 0.70-0.93, P = .003, I2 = 7%). Observational studies examining duration of cessation demonstrated that longer periods of cessation, compared with shorter periods, had an average reduction in total complications of 20% (RR 0.80, 95% CI, 3-33, P = .02, I2 = 68%).

      Conclusion

      Longer periods of smoking cessation decrease the incidence of postoperative complications.

      Keywords

      Tobacco smoking remains the leading cause of preventable death in the world.
      • Peto R.
      • Lopez A.D.
      • Boreham J.
      • Thun M.
      • Heath Jr, C.
      • Doll R.
      Mortality from smoking worldwide.
      Smoking cessation is associated with important benefits at individual and societal levels. Given the prevalence of smoking, considerable efforts have been directed toward developing interventions to assist smokers in quitting.
      • Wu P.
      • Wilson K.
      • Dimoulas P.
      • Mills E.J.
      Effectiveness of smoking cessation therapies: a systematic review and meta-analysis.
      The role of smoking cessation benefits within specific disease classifications is becoming increasingly clear, with, for example, decreased morbidity and mortality among recent former smokers compared with continuing smokers with cardiovascular diseases.
      • Wilson K.
      • Gibson N.
      • Willan A.
      • Cook D.
      Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.
      • Smoking cessation before any type of surgery reduced risks of complications, including wound healing and pulmonary complications.
      • Longer periods of smoking cessation before surgery demonstrated a significantly larger reduction in complications.
      • Meta-analysis of randomized trials showed a relative risk reduction of 41% (95% confidence interval, 15-59, P = .01) for prevention of postoperative complications. This was supported with observational data examining total complications, wound healing, and pulmonary complications.
      There has been a recent emerging body of evidence showing the benefit of preoperative and long-term postoperative smoking cessation.
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      • Moller A.
      • Tonnesen H.
      Risk reduction: perioperative smoking intervention.
      In the United States, an estimated 53.3 million surgical and nonsurgical procedures are performed annually.
      • Warner D.O.
      • Patten C.A.
      • Ames S.C.
      • Offord K.P.
      • Schroeder D.R.
      Effect of nicotine replacement therapy on stress and smoking behavior in surgical patients.
      Approximately 8 to 10 million procedures requiring surgery and anesthesia are performed on cigarette smokers.
      • Graham-Garcia J.
      • Heath J.
      Urgent smoking cessation interventions: enhancing the health status of CABG patients.
      • Abidi N.A.
      • Dhawan S.
      • Gruen G.S.
      • Vogt M.T.
      • Conti S.F.
      Wound-healing risk factors after open reduction and internal fixation of calcaneal fractures.
      Smokers may be at a greater risk of postoperative complications than nonsmokers, including delayed wound healing, pulmonary complications, and mortality.
      • Hall M.J.
      • Lawrence L.
      Ambulatory surgery in the United States, 1996.
      Preoperative smoking cessation seems to offer important benefits in reducing complications, although the duration of cessation required and the success of different interventions are not understood.
      • Russell M.A.
      • Stapleton J.A.
      • Feyerabend C.
      • et al.
      Targeting heavy smokers in general practice: randomised controlled trial of transdermal nicotine patches.
      Clinical trials have evaluated smoking-cessation interventions at varying times before surgery and found clinically meaningful reductions in complications.
      • Peto R.
      • Lopez A.D.
      • Boreham J.
      • Thun M.
      • Heath Jr, C.
      • Doll R.
      Mortality from smoking worldwide.
      • Wu P.
      • Wilson K.
      • Dimoulas P.
      • Mills E.J.
      Effectiveness of smoking cessation therapies: a systematic review and meta-analysis.
      • Wilson K.
      • Gibson N.
      • Willan A.
      • Cook D.
      Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.
      Trials also have evaluated both longer-
      • Wilson K.
      • Gibson N.
      • Willan A.
      • Cook D.
      Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies.
      and shorter-term cessation,
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      including as late as the day of surgery.
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      We aimed to determine the strength of evidence supporting the role of smoking cessation and the duration of cessation required in preventing postoperative complications by undertaking a systematic review and meta-analysis of observational studies and randomized trials.

      Materials and Methods

      Eligibility Criteria

      We included both observational studies and randomized trials that evaluated the incidence of postoperative complications among populations who achieved smoking abstinence at a defined time point before surgery. We included any classification of cessation and any surgical populations. Studies had to report the proportion of clinical complications of past smokers and current smokers.

      Study End Points

      Our primary study outcome was postoperative complications defined as total complications. Secondary outcomes included any wound healing complications, pulmonary or respiratory complications, all-cause mortality, and all-cause length of hospital stay. When a primary complication was distinct and total complications were not reported (eg, wound healing), we did not combine them as a composite.

      Search Strategy

      In consultation with a medical librarian, we established a search strategy. We searched independently, in duplicate, the following 10 databases (from inception to September 2009): MEDLINE, EMBASE, Cochrane CENTRAL, AMED, CINAHL, TOXNET, Development and Reproductive Toxicology, Hazardous Substances Databank, PsycINFO, and Web of Science. Given that observational studies are poorly indexed in many databases, we also searched databases that include the full text of journals (ScienceDirect, and Ingenta, including articles in full text from ∼1700 journals since 1993).
      • Kuper H.
      • Nicholson A.
      • Hemingway H.
      Searching for observational studies: what does citation tracking add to PubMed? A case study in depression and coronary heart disease.
      In addition, we searched the bibliographies of published relevant reviews and health technology assessments.
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      NICE: TA39
      Smoking cessation - bupropion and nicotine replacement therapy: Guidance Issue Date: March 2002 Review Date: March 2005.
      • Theadom A.
      • Cropley M.
      Effects of preoperative smoking cessation on the incidence and risk of intraoperative and postoperative complications in adult smokers: a systematic review.
      • Cropley M.
      • Theadom A.
      • Pravettoni G.
      • Webb G.
      The effectiveness of smoking cessation interventions prior to surgery: a systematic review.
      Searches were not limited by language, sex, or age.

      Study Selection

      Two investigators working independently, in duplicate, scanned all abstracts and obtained the full-text reports of records indicating that the study is an original research article evaluating the impact of smoking cessation on the outcomes of interest. After obtaining full reports of candidate studies (in full peer-reviewed publication or media article), the same reviewers independently assessed eligibility from full-text papers.

      Data Collection

      Two reviewers conducted data extraction independently using a standardized pre-piloted form (available from the authors on request). Reviewers collected information about the smoking intervention tested, the population studied (age, sex, underlying conditions, and types of surgery), the treatment dosages and dosing schedules, the relative effectiveness of treatments begun at any time points before surgery, the specific measurement of abstinence (sustained or point-prevalence), and the biochemical confirmation of smoking status. Study evaluation assessed risk of bias per a modified Cochrane risk-of-bias tool and included general methodological quality features specific to randomized trials, including allocation concealment, sequence generation, blinding status, intention-to-treat, sources of funding, and appropriate descriptions of loss to follow-up.
      • Lundh A.
      • Gotzsche P.C.
      Recommendations by Cochrane Review Groups for assessment of the risk of bias in studies.
      In addition, for nonrandomized evaluations, we applied the Newcastle-Ottawa Scale to evaluate the reporting rigor of observational studies.
      • Wells G.A.
      • Shea B.
      • O'Connell D.
      • et al.
      The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
      The Newcastle-Ottawa Scale is a scoring checklist addressing issues of design and implementation of a cohort or case-control, including issues of selection of participants, comparability of cases and controls, exposure, and outcomes. We entered the data into an electronic database, such that duplicate entries existed for each study; when the 2 entries did not match, differences were resolved through discussion and third-party arbitration.

      Data Analysis

      To assess inter-rater reliability on inclusion of articles, we calculated the Phi statistic, which provides a measure of interobserver agreement independent of chance.
      • Meade M.O.
      • Guyatt G.H.
      • Cook R.J.
      • et al.
      Agreement between alternative classifications of acute respiratory distress syndrome.
      We calculated the relative risk (RR) and appropriate 95% confidence intervals (CIs) of outcomes according to the number of complications reported in the original studies or substudies. Relative risks are typically a more clinically understood effect measure than odds ratios but cannot be used with some observational designs (eg, case-control studies). In circumstances of zero outcome events in one arm of a trial, we planned to apply the Haldane approach and add 0.5 to each arm, as suggested by Sheehe.
      • Sheehe P.R.
      Combination of log relative risk in retrospective studies of disease.
      We applied the modified intent-to-treat principal, whereby a patient must receive at least 1 dose of the study intervention, in this case, surgery. We first pooled all randomized trials. We used the DerSimonian–Laird random effects method to pool studies,
      • Fleiss J.L.
      The statistical basis of meta-analysis.
      which recognizes and anchors studies as a sample of all potential studies, and incorporates an additional between-study component to the estimate of variability.
      • DerSimonian R.
      • Laird N.
      Meta-analysis in clinical trials.
      We also calculated the I2 statistic for each analysis as a measure of the proportion of the overall variation that is attributable to between-study heterogeneity.
      • Higgins J.P.
      • Thompson S.G.
      Quantifying heterogeneity in a meta-analysis.
      We performed a sensitivity analysis to examine shorter-term (<4 weeks) and longer-term (>4 weeks) effects, and to examine intensive versus passive interventions, as defined by Thomsen et al.
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      We performed a meta-regression to examine the impact of time, in weeks, on log RR effect size. We display forest plots for our primary analysis, showing individual study effect measures with 95% CIs, and the overall DerSimonian–Laird pooled estimate and the regression plot with circle size conferring study sample size. For observational studies reporting total complications, we pooled the proportions of past smokers and current smokers by stabilizing the variances of the raw proportions (r/n) using a Freeman-Tukey type arcsine square root transformation and applying a random effects model.
      • Paoletti P.
      • Fornai E.
      • Maggiorelli F.
      • et al.
      Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch.
      • Campbell I.A.
      • Prescott R.J.
      • Tjeder-Burton S.M.
      Smoking cessation in hospital patients given repeated advice plus nicotine or placebo chewing gum.
      Although several methods of pooling proportions exist,
      • Wetterslev J.
      • Thorlund K.
      • Brok J.
      • Gluud C.
      Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis.
      the Freeman–Tukey method works well with both fixed and random effects meta-analysis and truncates at zero (because it is impossible to have less than zero events).
      • Mills E.J.
      • Wu P.
      • Spurden D.
      • Ebbert J.O.
      • Wilson K.
      Efficacy of pharmacotherapies for short-term smoking abstinance: a systematic review and meta-analysis.
      Where appropriate, we pooled using random effects RR. All P values are exact to < .001. We considered P < .05 as significant. Analyses were conducted using StatsDirect (version 2.5.2, www.statsdirect.com) and Comprehensive Meta-analysis (version 2, www.meta-analysis.com).

      Results

      Results of the Literature Search

      We reviewed 847 abstracts that met our search criteria. During the initial title and abstract selection process, we excluded 772 abstracts for reasons identified in Figure 1. The search was sensitive and not initially specific. Of those excluded, 139 abstracts were either non-human studies or non-English abstracts, 399 abstracts did not address the review topic, and a further 234 were review articles. We then obtained the full-text papers of the remaining 75 abstracts, and these proceeded to the full-text review stage. After rigorous screening of the 75 full-text articles, 30 of them satisfied the study inclusion criteria and were included in the initial review (Phi > 0.8). We then excluded 9 observational studies because of errors in the reporting of relevant outcome data per arm
      • Lavernia C.J.
      • Sierra R.J.
      • Gomez-Marin O.
      Smoking and joint replacement: resource consumption and short-term outcome.
      and failing to report differences between past and current smokers on the outcomes of interest to the review.
      • Goodwin S.J.
      • McCarthy C.M.
      • Pusic A.L.
      • et al.
      Complications in smokers after postmastectomy tissue expander/implant breast reconstruction.
      • Brooks-Brunn J.A.
      Predictors of postoperative pulmonary complications following abdominal surgery.
      • Dixon A.J.
      • Dixon M.P.
      • Dixon J.B.
      • Del Mar C.B.
      Prospective study of skin surgery in smokers vs nonsmokers.
      • Glassman S.D.
      • Anagnost S.C.
      • Parker A.
      • Burke D.
      • Johnson J.R.
      • Dimar J.R.
      The effect of cigarette smoking and smoking cessation on spinal fusion.
      • Moore S.
      • Mills B.B.
      • Moore R.D.
      • Miklos J.R.
      • Mattox T.F.
      Perisurgical smoking cessation and reduction of postoperative complications.
      • Selber J.C.
      • Kurichi J.E.
      • Vega S.J.
      • Sonnad S.S.
      • Serletti J.M.
      Risk factors and complications in free TRAM flap breast reconstruction.
      • Williams G.
      • Daly M.
      • Proude E.M.
      • et al.
      The influence of alcohol and tobacco use in orthopaedic inpatients on complications of surgery.
      • Woehlck H.J.
      • Connolly L.A.
      • Cinquegrani M.P.
      • Dunning M.B.
      • Hoffmann R.G.
      Acute smoking increases ST depression in humans during general anesthesia.
      Our review thus includes 6 randomized trials
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      • Myles P.S.
      • Leslie K.
      • Angliss M.
      • Mezzavia P.
      • Lee L.
      Effectiveness of bupropion as an aid to stopping smoking before elective surgery: a randomised controlled trial.
      • Lindstrom D.
      • Sadr Azodi O.
      • Wladis A.
      • et al.
      Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.
      • Sorensen L.T.
      • Hemmingsen U.
      • Jorgensen T.
      Strategies of smoking cessation intervention before hernia surgery—effect on perioperative smoking behavior.
      • Moller A.M.
      • Villebro N.
      • Pedersen T.
      • Tonnesen H.
      Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
      and 15 observational studies.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      Figure thumbnail gr1
      Figure 1Flow diagram of study selection process. RCT = randomized clinical trial.

      Characteristics of Included Studies

      The majority of the studies were conducted in the United States.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      Four studies were performed in Denmark,
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      • Møller A.M.
      • Villebro N.
      • Pedersen T.
      • Tønnesen H.
      Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
      • Sorensen L.T.
      • Hemmingsen U.
      • Jorgensen T.
      Strategies of smoking cessation intervention before hernia surgery—effect on perioperative smoking behavior.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      2 studies were performed in Australia,
      • Myles P.S.
      • Leslie K.
      • Angliss M.
      • Mezzavia P.
      • Lee L.
      Effectiveness of bupropion as an aid to stopping smoking before elective surgery: a randomised controlled trial.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      3 studies were performed in Japan,
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      1 study was performed in Israel,
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      and 1 study was performed in Sweden.
      • Lindström D.
      • Azodi O.S.
      • Wladis A.
      • et al.
      Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.
      Of the 21 included studies, 6 were randomized trials,
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      • Myles P.S.
      • Leslie K.
      • Angliss M.
      • Mezzavia P.
      • Lee L.
      Effectiveness of bupropion as an aid to stopping smoking before elective surgery: a randomised controlled trial.
      • Møller A.M.
      • Villebro N.
      • Pedersen T.
      • Tønnesen H.
      Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
      • Sorensen L.T.
      • Hemmingsen U.
      • Jorgensen T.
      Strategies of smoking cessation intervention before hernia surgery—effect on perioperative smoking behavior.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      • Lindström D.
      • Azodi O.S.
      • Wladis A.
      • et al.
      Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.
      and the remaining were observational studies.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      Of the observational studies, 10 were prospective comparisons
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      and 5 were retrospective analyses of patients with complications.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      The included studies involved a heterogeneous array of surgical procedures, including lung,
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      orthopedic/bone and abdominal,
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      • Møller A.M.
      • Villebro N.
      • Pedersen T.
      • Tønnesen H.
      Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
      breast,
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      head/neck,
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      heart,
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      and various elective surgeries,
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      • Sorensen L.T.
      • Hemmingsen U.
      • Jorgensen T.
      Strategies of smoking cessation intervention before hernia surgery—effect on perioperative smoking behavior.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      • Lindström D.
      • Azodi O.S.
      • Wladis A.
      • et al.
      Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.
      and reported on postsurgical complications among study participants. Time of study follow-up ranged from 1 day to 57 months.

      Methodological Quality of Included Studies

      Table 1 shows the risk of bias characteristics of the randomized trials. In general, studies were well reported with a low risk of bias. Table 2 shows the Newcastle-Ottawa Scale risk of bias for observational studies. One of the observational studies did not clearly define the length of time that smokers/past smokers ceased smoking before the surgery was performed.
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      Seven studies did not specify the follow-up period.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      Table 1Risk of Bias Assessment: Randomized Clinical Trials
      First Author, YearReport Method of Sequence GenerationReport Efforts to Conceal AllocationReport Blinding Status of Groups or ResearchersRefusal Rate of Eligible ParticipantsIntent-to-Treat AnalysisFree of Selective ReportingLost to Follow-Up > 20%Study Funding Source(s)
      Lindstrom 2008+++39%++Public, industry provided drug
      Moller 2002+28%++Public, industry provided drug
      Myles 2004++++++Hospital, industry provided drug
      Sorensen 2003++25%++Public, industry provided drug
      Sorensen 2007++9%++Public, industry
      Warner 2005+_+4%++Public, industry provided drug
      + = clear; − = unclear or negative.
      Table 2Risk of Bias Tables: Observational Studies
      Definition requires classification according to studied groups.
      ,
      Versus NS.
      First Author, YearAdequate Case/Control/Group Definition?Potential for Bias in Case/Group RepresentationPresence of Controls/Comparison Group?Comparability among GroupsAscertainment of ExposureCessation Validation MethodNon-Response RatesAssessment of OutcomeSufficient Follow-Up for Outcome Occurrence?Adequacy of Follow-Up (Rates)
      Barrera 2005YesYesYesPQ were significantly older than NS.Self-reportSelf-report via questionnaireNot applicableIndependentYes>80%
      Bluman 1998YesYesYesCS were significantly younger than PS or NS.Self-reportSelf-report via questionnaireNot applicableIndependent (medical records)Yes>80%
      Chang 2000YesYesYesNo significant difference among groups.Not specifiedMedical recordsNot applicableIndependent (medical records)Unclear>80%
      Goodwin 2005YesYesYesNo major significant demographic differences except for the higher proportion of NS with stage 0 disease.Self-reportSelf-reportNot applicableIndependent (medical records)Yes>80%
      Kuri 2005YesYesYesNS were more likely to be female, and LQ were significantly younger than EQ.Self-reportComparison of 3 self-reportsNot applicableIndependent (medical records), self-reportsUnclearUnclear
      Levin 2004YesYesYes; groups were undefined by their percentages relative to sample sizeNo significant difference among groups in terms of age and gender.Medical recordsMedical recordsNot applicableIndependent (medical records)Yes>80%
      Mason 2009YesYesYesNS were more likely to be female.Medical recordsMedical recordsNot applicableIndependent (medical records)Unclear>80%
      Myles 2002YesYesYesCS were younger than PS or NS.Self-reportExhaled air CONot applicableIndependent (medical records), self-reportsNo>80%
      Nakagawa 2001YesYesYesSimilar demographics among groups.Self-reportMedical records, Self-reportNot applicableIndependent (medical records), self-reportUnclear>80%
      Padubidri 2001YesYesYesTRAM flap surgery was used more in NS, and tissue expander method was used more often in smokers.Medical recordsMedical recordsNot applicableIndependent (medical records)Unclear>80%
      Sorensen 2005YesYesYesBaseline demographics among groups were unreported.Self-reportMedical records, validated by a second self-report during follow-upNot applicableIndependent (medical records)Yes>80%
      Taber 2009YesYesYesCS had 1 y less of education and more alcohol use than other groups.Self-reportSelf-reportNot applicableIndependent (medical records)Unclear>80%
      Vaporciyan 2002YesYesYesGroups differed significantly in age, sex, and disease type.Medical recordsMedical recordsNot applicableIndependent (medical records)Yes>80%
      Warner 1984YesYesYesBaseline demographics among groups were unreported.Self-reports, medical recordsMedical recordsNot applicableIndependent (medical records)Yes>80%
      Warner 1989YesYesYesBaseline demographics among groups were unreported.Self-report, medical recordsUrinary cotinine analysisNot applicableIndependent (medical records)Yes>80%
      Yamashita 2004YesYesYesCS were younger than PS or NS.Self-reportSelf-reportNot applicableIndependentYes>80%
      CO = carbon monoxide; CS = current smoker; EQ = early quitters; LQ = late quitters; NS = nonsmoker; PS = past smoker; TRAM = transverse rectus abdominis myocutaneous.
      Note: The Newcastle-Ottawa Scale was used to assess observational studies.
      low asterisk Definition requires classification according to studied groups.
      Versus NS.

      Meta-analysis of Effectiveness

      We pooled 6 randomized trials evaluating varied smoking interventions on total complications (Table 3, Table 4).
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      • Myles P.S.
      • Leslie K.
      • Angliss M.
      • Mezzavia P.
      • Lee L.
      Effectiveness of bupropion as an aid to stopping smoking before elective surgery: a randomised controlled trial.
      • Lindstrom D.
      • Sadr Azodi O.
      • Wladis A.
      • et al.
      Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.
      • Sorensen L.T.
      • Hemmingsen U.
      • Jorgensen T.
      Strategies of smoking cessation intervention before hernia surgery—effect on perioperative smoking behavior.
      • Moller A.M.
      • Villebro N.
      • Pedersen T.
      • Tonnesen H.
      Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
      We found a pooled RR of 0.59 (95% CI, 0.41-0.85, P = .01, I2 = 14%; Figure 2). Our meta-regression analysis found that each week of cessation resulted in a larger effect size (B coefficient −0.191, 95% CI, −0.368 to −0.014, P = .03; Figure 3). We performed a sensitivity analysis evaluating short-term studies (<4 weeks)
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      (RR 0.92, 0.53-1.60, P = .78) versus longer cessation (RR 0.45, 95% CI, 0.30-0.68, P < .001, I2 = 0%) (P value for difference .041). We also examined the use of intensive
      • Sorensen L.T.
      • Jorgensen T.
      Short-term pre-operative smoking cessation intervention does not affect postoperative complications in colorectal surgery: a randomized clinical trial.
      • Lindstrom D.
      • Sadr Azodi O.
      • Wladis A.
      • et al.
      Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial.
      • Moller A.M.
      • Villebro N.
      • Pedersen T.
      • Tonnesen H.
      Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial.
      (RR 0.55, 95% CI, 0.31-0.98, P = .04, I2 = 61%) versus less intensive (RR 0.78, 95% CI, 0.34-1.80, P = .56, I2 = 0%) interventions (P value for difference .49).
      Table 3Characteristics of Included Randomized Trials
      First Author, YearType of StudyTypes of SurgeryIntervention and Control InterventionsSample SizeMale (%)Mean Age (y)Cessation Period Defined Clearly?Cessation Validation MethodPre-surgery Smoking Cessation PeriodCessation Intervention (and Period Pre-surgery)Follow-up Period Postsurgery
      Lindstrom 2008RCTHernia repair, laparoscopic cholecystectomy, hip/knee prosthesisIG = 47%; smokers who received an intervention to keep them smoke-free from 4 wk preoperatively to 4 wk postoperatively

      CG = 53%; smokers who did not receive any such intervention for smoking cessation pre-surgery

      In per protocol analysis, smokers were grouped as:

      1. Smokers who quit ≥ 3 wk preoperatively and 4 wk postoperatively

      2. Smokers who quit 1-2 wk preoperatively and 4 wk postoperatively

      3. Smokers who continued smoking or only reduced smoking
      1025355YesSelf-report and COIG: smoke-free from 4 wk preoperatively to 4 wk postoperatively

      In per-protocol analysis groups:

      group 1, ≥3 wk preoperatively and 4 wk postoperatively;

      group 2, 1-2 wk preoperatively and 4 wk postoperatively;

      group 3, cessation period undefined
      Yes; individual counseling, telephone hotline, and free nicotine substitution (nicotine replacement therapy) for 4 wk pre-surgery30 d
      Moller 2002RCTHip or knee replacementIG = 52%; defined as smokers who received an intervention to keep them smoke-free or help reduce smoking by 50% from 6-8 wk preoperatively

      CG = 48%; defined as smokers who did not receive any such intervention for smoking cessation pre-surgery
      10842.665YesExhaled air CO6-8 wk pre-surgery and 10 d postsurgeryYes; information and weekly counseling for 6-8 wk pre-surgery4 wk
      Sorensen 2003RCTColorectal surgeryIG: 47%; defined as smokers who received an intervention to keep them smoke-free or reduce their smoking 2-3 wk pre-surgery and until sutures were removed

      CG: 53%; defined as smokers who did not receive any such intervention and were asked to maintain their daily smoking habits
      576565.5 (median)YesSelf-report, exhaled air CO; salivary cotinineIG: advised to be smoke-free or reduced smoking from 2-3 wk pre-surgeryYes; counseling and nicotine replacement therapy30 d
      Sorensen 2007RCTElective open incisional or inguinal herniotomyIG: 70%; defined as smokers who received an intervention by means of an advice and reminder to stop smoking at least 1 mo pre-surgery and until sutures were removed

      CG: 30%; defined as smokers who did not receive any such intervention
      21384.554.6 (median)YesSelf-report, exhaled air CO; salivary cotinineIG: advised to stop smoking at least 1 mo pre-surgeryYes; 3 levels: advice only, advice and telephone reminder, advice and reminder and outpatient nicotine substitution demonstration3 mo
      Myles 2004RCTGeneral, orthopedic, urologic, ear, nose, throat, faciomaxillaryIG: Bupropion 7 wk before expected surgery (150 mg bid) + 1 telephone counseling.

      CG: placebo + 1 telephone counseling
      476645YesExhaled air COBoth groups 7 wk pre-surgeryBupropion (150 mg bid)6 mo
      Warner 2005RCTOrthopaedic, intra-abdominal, spinal, genitourinary, otorhinolaryngologic, gynecologic, otherIG: nicotine patch applied on day of surgery

      CG: placebo patch
      1214847YesExhaled air COBoth groups, day of surgeryNicotine patch applied on day of surgery1 mo
      RCT = randomized clinical trial; IG = intervention group; CG = control group; CO = carbon monoxide.
      Table 4Effects of Randomized Trials on Perioperative Complications
      First Author, YearIntensity of Preoperative Smoking InterventionDefinition of Perioperative ComplicationRelative Risk (95% CI) for Perioperative Complications
      Lindstrom 2008IntensiveEvents causing additional medical or surgical treatment or investigation, prolonged hospital stay, unscheduled postoperative checkups within 30 d

      Any wound complication
      • 0.51 (0.27-0.97)
      • 0.49 (0.20-1.16)
      Moller 2002IntensiveDeath or postoperative morbidity requiring treatment within 30 d

      Wound healing complications
      • 0.34 (0.19-0.64)
      • 0.17 (0.05-0.56)
      Myles 2004Less intensivePostoperative wound infections0.82 (0.06-11.33)
      Sorensen 2003IntensiveAdverse events within 30 d requiring medical or surgical intervention0.94 (0.51-1.73)
      Sorensen 2007Less intensePostoperative wound infection with swollen or infected wound or medical intervention required at suture removal0.71 (0.21-2.41)
      Warner 2005Less intensiveSerious postoperative adverse events0.86 (0.24-3.03)
      CI = confidence interval.
      Figure thumbnail gr2
      Figure 2Forst plot of randomized clinical trials on total complications.
      Figure thumbnail gr3
      Figure 3Meta-regression plot, effect of time of cessation on complications.

      Observational Studies

      Risk of Total Postoperative Complications

      Table 5, Table 6 (available online) show the characteristics and outcomes of the 15 observational studies. Thirteen observational studies
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      provided sufficient details of general complications occurring between past smokers and current smokers. We were able to pool data from 12 of these studies.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Levin L.
      • Herzberg R.
      • Dolev E.
      • Schawartz-Arad D.
      Smoking and complications of onlay bone grafts and sinus lift operations.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      (One study presented data only as adjusted odds and was excluded.)
      • Sorensen L.T.
      • Hemmingsen U.B.
      • Kirkeby L.T.
      • Kallehave F.
      • Jorgensen L.N.
      Smoking is a risk factor for incisional hernia.
      There was a statistically significant reduction in the risk of total complications in former smokers compared with current smokers, with an average 22% (95% CI, 13-34) of former smokers experiencing an event compared with 32% (95% CI, 19-47) of current smokers (RR 0.76, 95% CI, 0.69-0.84, P < .0001, I2 = 15%).
      Table 5Characteristics of Included Observational Studies
      Definition requires classification according to studied groups.
      ,
      Versus NS.
      First AuthorType of StudyPrimary Surgery TypeStudied Group According to Smoking StatusSample SizeMale (%)Mean Age (y)Cessation Period Defined Clearly?
      Definition requires classification according to studied groups.
      Cessation Validation MethodPre-surgery Smoking Cessation PeriodCessation Intervention (and Period Pre-surgery)Follow-up Period Postsurgery
      Barrera 2005CohortLung tumor resection/thoracotomyNS = 21%

      PS =

      EQ: defined as those who quit smoking > 2 mo pre-surgery = 62%

      LQ: defined as those who quit smoking ≤ 2 mo, but > 1 wk pre-surgery = 13%

      CS = 4%
      3004864 ± 12YesSelf-report via questionnaireEQ quit smoking for > 2 mo pre-surgery

      LQ quit smoking for ≤ 2 mo, but > 1 wk pre-surgery
      No30 d
      Bluman 1998CohortGeneral, orthopedic, urologic or cardiovascular elective surgeryNS = 20%

      PS = 46%; defined as those who smoked > 2 wk pre-surgery

      CS = 34%; defined as those who smoked ≤ 2 wk pre-surgery
      4109759.5YesSelf-report via questionnairePS: >2 wk pre-surgery

      CS: ≤2 wk pre-surgery
      NoNR
      Chang 2000CohortBreast reconstruction with TRAM flapsNS: 67%

      PS: defined as those who quit smoking at least 4 wk pre-surgery = 21%

      CS = 13%
      718NRNot specifiedYesMedical recordsPS: quit smoking at least 4 wk pre-surgeryNoNR
      Goodwin 2005CohortTissue expander/implant breast reconstructionNS = 74%

      PS = 15%; defined as those who quit smoking > 4 wk pre-surgery

      CS = 11%; defined as having continued or stopped smoking < 4 wk pre-surgery
      515047YesSelf-reportPS = stopped smoking > 4 wk pre-surgery

      CS = continued or stopped smoking < 4 wk pre-surgery
      No20 mo
      Kuri 2005CohortReconstructive head and neck surgeryNS = 21%

      PS =

      LQ = 18%; defined as smoking within 8-21 d pre-surgery

      IQ = 11%; defined as smoking within 22-42 d pre-surgery

      EQ = 35%; defined as smoking within ≥ 43 d pre-surgery

      CS = 15%; defined as smoking within 7 d pre-surgery
      18879.859YesComparison of 3 self-reportsLQ: smoking within 8-21 d pre-surgery

      IQ: smoking within 22-42 d pre-surgery

      EQ: smoking within 43 d or longer pre-surgery

      CS = smoking within 7 d pre-surgery
      NoNR
      Levin 2004CohortOnlay bone graft, sinus liftPS: patients who quit smoking for ≥ 6 mo pre-surgery

      MS: CS smoking < 10 cigarettes/d and smoking history < 10 y

      HS: CS smoking > 10 cigarettes/d and smoking history > 10 y

      Groups were undefined by their percentages relative to sample size
      12833.6NRYesMedical recordsPS: quit smoking for ≥ 6 mo pre-surgeryNo≥6 mo postsurgery
      Mason 2009CohortLung resectionsNS = 21%; defined as never smokers or those who smoked < 100 cigarettes in their lifetime

      PS: LQ = 5.1%; defined as those who quit smoking for > 14 d to 1 mo pre-surgery

      IQ = 12%; defined as those who quit 1-12 mo pre-surgery

      EQ = 50%; defined as those who quit smoking > 12 mo pre-surgery

      CS = 20%; defined as smoking within 14 d pre-surgery
      799048.366YesMedical recordsPS = LQ: quit smoking for > 14 d to 1 mo pre-surgery

      IQ: quit smoking 1-12 mo pre-surgery

      EQ: quit smoking > 12 mo pre-surgery

      CS = smoking within 14 d pre-surgery
      NoNR
      Myles 2002CohortAmbulatory surgeryNS = 35%; defined as never smokers with a COexp of ≤ 10 ppm

      PS = 24%; defined as those who quit smoking for > 28 d pre-surgery

      CS = 41%; defined as CS or with COexp of > 10 ppm
      4893839YesSelf-report and CO analysisPS = quit smoking for > 28 d pre-surgeryNo7 d
      Nakagawa 2001CohortPulmonary surgeryNS = 41%

      PS =

      RS = 5%; defined as those who quit smoking 2-4 wk pre-surgery

      ES = 42%; defined as those who quit smoking for > 4 wk pre-surgery

      CS = 13%; defined as those who smoked within 2 wk pre-surgery
      2885861.5YesMedical records, self-reportPS =

      RS = 2-4 wk pre-surgery

      ES = >4 wk pre-surgery

      CS = within 2 wk pre-surgery
      NoNR
      Padubidri 2001CohortPostmastectomy breast reconstructionNS = 69%; defined as those who had never smoked

      PS = 10%; defined as previous smokers who quit smoking ≥ 3 wk pre-surgery

      CS = 21%; defined as those who were still smoking at the time of surgery
      748049.2YesMedical recordsPS: quit smoking ≥ 3 wk pre-surgeryYes; quitting smoking was advised during enrolment at clinicNR
      Sorensen 2005CohortElective and emergency laparotomiesNS = 29%

      PS = 29%; defined as those who previously smoked but quit sometime pre-surgery

      CS = 42%; defined as those who smoked at time of surgery and at follow-up
      31045.564.6 (median)NoMedical records, validated by a second self-report during follow-upNot specifiedNo33-57 mo
      Taber 2009CohortLaparoscopic donor nephrectomyNS = 63%; defined as never smokers

      PS = 18%; defined as those who previously smoked but quit at least 2 wk pre-surgery

      CS = 19%; defined as those who smoked up to the surgery day
      2214539YesSelf-reportPS: quit at least 2 wk pre-surgeryNoNR
      Vaporciyan 2002CohortPneumonectomyNS = 13%

      S =

      LQ = 23%; defined as persons who quit smoking < 1 mo pre-surgery

      EQ = 63%; defined as those who quit smoking ≥ 1 mo pre-surgery
      25769.660 ± 10 (median)YesMedical recordsLQ: quit < 1 mo pre-surgery

      EQ: quit ≥ 1 mo pre-surgery
      No30 d
      Warner 1984CohortCoronary artery bypass graftingNS = 9%

      CS = 25%; defined as those who never stopped smoking pre-surgery

      Stopped smoking < 2 wk pre-surgery = 17%

      Stopped smoking 2-4 wk pre-surgery = 9%

      Stopped smoking 4-8 wk pre-surgery = 6%

      Stopped smoking > 8 wk pre-surgery = 35%
      5007758.2YesMedical recordsGroup 1: smokers who stopped < 2 wk pre-surgery

      Group 2: smokers who stopped 2-4 wk pre-surgery

      Group 3: smokers who stopped 4-8 wk pre-surgery

      Group 4: smokers who stopped > 8 wk pre-surgery
      No30 d
      Warner 1989CohortCoronary artery bypass graftingNS = 22%; defined as those who had never smoked and assigned a smoke-free day of 150

      PS = 69%; defined as previous smokers who quit smoking sometime in the past, and this group includes LQ = 11%, defined as those who quit ≤ 8 wk pre-surgery, EQ = 58%, defined as those who quit > 8 wk pre-surgery, and CS = 9%, defined as those with cotinine levels > 0.5 μg/mL and assigned a smoke-free day of −1
      1928364YesUrinary cotinine analysisAmong PS,

      LQ: quit ≤ 8 wk pre-surgery

      EQ: quit > 8 wk pre-surgery
      No1 y (via correspondence)
      Yamashita 2004CohortElective minor surgeriesNS = 48%; defined as those who had never smoked

      PS = 37%; defined as smokers who quit smoking < 2 d pre-surgery

      CS = 16%; defined as smokers who smoked until 1 d pre-surgery
      100852.653YesSelf-report via interviewPS: quit smoking < 2 d pre-surgery

      CS: quit smoking > 1 d pre-surgery
      No30 d or until discharge
      CO = carbon monoxide; CS = current smoker; EQ = early quitters; ES = ex-smoker; HS = heavy smoker; IQ = intermediate quitters; LQ = late quitters; MS = mild smoker; NR = not reported; NS = nonsmoker; ppm = packs per month; PS = past smoker; RR = relative risk; RS = recent smoker; TRAM = transverse rectus abdominis myocutaneous; β = group numbers presented do not sum up to total N.
      low asterisk Definition requires classification according to studied groups.
      Versus NS.
      Table 6Effects of Smoking Cessation in Observational Studies
      Definition requires classification according to studied groups.
      ,
      Versus NS.
      First AuthorStudied Group According to Smoking StatusSample SizeMale (%)Complication Risk/Percentage Risk/Relative Risk/Odds RatioImportant Findings
      Barrera 2005NS = 21%

      PS =

      EQ: defined as those who quit smoking > 2 mo pre-surgery = 62%

      LQ: defined as those who quit smoking ≤ 2 mo but > 1 wk pre-surgery = 13%

      CS = 4%
      30048% Overall complications and 95% CI

      NS = 8% (1.24-14.38)

      PS = 19% (14.1-24.46)

      CS = 23% (0.18-45.98)

      % Pneumonia and 95% CI

      NS = 3% (−1.14 to 7.4)

      PS = 11% (6.69-14.83)

      CS = 23% (0.18-45.98)

      % Atelectasis and 95% CI

      NS = 0%

      PS = 5% (2.09-7.77)

      CS = 0% Mean hospital length of stay (d)

      NS = 6

      PS = 8

      CS = 9
      Overall pulmonary complications and pneumonia incidence were higher among CS compared with PS and NS.

      CS had longer hospital stays than PS and NS.

      PQ (>2 mo quit time) had fewer complications compared with recent quitters (≤2 mo, >1 wk quit time).
      Bluman 1998NS = 20%

      PS = 46%; defined as smoking > 2 wk pre-surgery

      CS = 34%; defined as smoking ≤ 2 wk pre-surgery
      41097% Any complications and 95% CI

      NS = 5% (0.22-9.54)

      PS = 13% (8.04-17.62)

      CS = 22% (15.15-28.83)

      % Pulmonary infections and 95% CI

      NS = 0%

      PS = 1% (−0.4 to 2.54)

      CS = 3% (0.1-5.58)

      % Atelectasis and 95% CI

      NS = 4% (−0.4 to 7.72)

      PS = 7% (3.72-11.26)

      CS = 8% (3.37-12.23)

      % Hospital readmission for pneumonia and 95% CI

      NS = 1% (−1.16 to 3.6)

      PS = 0

      CS = 1% (−0.68 to 2.1)

      % Mortality due to pulmonary disease and 95% CI

      NS = 0

      PS = 1%

      CS = 1% (−0.51 to 1.57)
      Postsurgical pulmonary complication risk was 6× higher in CS compared with NS (OR 5.5, CI, 1.9-16.2).

      CS who reduced smoking pre-surgery were 7× more likely to develop postsurgical pulmonary complications compared with those who did not reduce smoking.

      Among those reducing cigarette smoking ≤ 1 mo pre-surgery, those who reduced closest to surgery were at greatest risk of developing complications.
      Chang 2000NS: 67%

      PS: defined as persons who quit smoking at least 4 wk pre-surgery = 21%

      CS = 13%
      718NR% Overall flap necrosis and 95% CI

      NS: 22.6% (18.8-26.3)

      PS: 25.3% (18.4-32.3)

      CS: 31.1% (21.6-40.7)

      % Mastectomy skin flap necrosis and 95% CI

      NS: 9% (6.4-11.6)

      PS: 10% (5.2-14.8)

      CS: 18.9% (10.8-27.0)

      % Flap fat necrosis and 95% CI

      NS: 6.5% (4.3-8.7)

      PS: 8.7% (4.2-13.2)

      CS: 7.8% (2.3-13.3)
      PS who quit smoking at least 4 wk pre-surgery have reduced postsurgical complications compared with CS.

      Smokers with a smoking history of > 10 pack-y were at an increased risk of perioperative complications compared with those with < 10 pack-y.

      CS were at a higher risk of mastectomy skin flap necrosis than NS.
      Goodwin 2005NS = 74%

      PS = 15%; defined as having stopped smoking > 4 wk pre-surgery

      CS = 11%; defined as having continued or stopped smoking < 4 wk pre-surgery
      5150Comparison is between NS and smokers (CS + PS)

      % Total complications and 95% CI

      NS = 15.1% (11.6-18.7)

      CS = 37.9% (29.6-46.16)

      % Reconstructive failure and 95% CI

      NS = 1.6% (0.34-2.86)

      CS = 5.3% (1.48-9.12)

      % Skin flap necrosis and 95% CI

      NS = 6.5% (4.03-8.97)

      CS = 16.7% (10.31-23.03)

      % Infection and 95% CI

      NS = 2.9% (1.22-4.58)

      CS = 9.1% (4.19-14.01)
      Because there was no difference in the overall complication rates in PS and CS (39.7% vs 36.5%), PS were therefore considered as part of CS in the comparisons.

      In comparison with NS, smokers were 3× more likely to experience a complication postsurgery.

      A positive relationship was observed between cigarette ppd and overall complications (OR 1.80; 95% CI, 1.00-3.34).

      A similar relationship also was seen between duration of smoking history and overall complications.
      Kuri 2005NS = 21%

      PS =

      LQ = 18%; defined as smoking within 8-21 d pre-surgery

      IQ = 11%; defined as smoking within 22-42 d pre-surgery

      EQ = 35%; defined as smoking within ≥ 43 d pre-surgery

      CS = 15%; defined as smoking within 7 d pre-surgery
      18879.8% Incidence of impaired wound healing and 95% CI

      NS: 47.5% (32-63)

      PS:

       LQ = 67.6% (52-83)

       IQ = 55.0% (33-77)

       EQ = 59.1% (47-71)

      CS: 85.7% (73-97)

      Risk of impaired wound healing development (OR and 95% CI) among study groups

      NS: 0.11 (0.03-0.51)

      PS:

       LQ = 0.31 (0.08-1.24)

       IQ = 0.17 (0.04-0.75)

       EQ = 0.17 (0.05-0.60)
      This study suggests that a 3-wk smoke-free period pre-surgery can reduce the incidence of impaired wound healing among patients undergoing reconstructive head and neck surgery.

      The data suggest that smoking cessation for ≥ 3 wk before reconstructive head and neck surgery can provide benefits for smokers, regardless of the level of cigarette consumption.
      Levin 2004PS: patients who quit smoking for ≥ 6 mo pre-surgery

      MS: CS smoking < 10 cigarettes/d and smoking history < 10 y

      HS: CS smoking > 10 cigarettes/d and smoking history > 10 y

      Groups were undefined by their percentages relative to sample size
      12833.6% Total complications and 95% CI (patients with onlay graft)

      PS: 23.1% (11.63-34.53)

      CS: 50% (21.71-78.29)

      % Total complications and 95% CI (patients with sinus lift)

      PS: 63.3% (49.77-76.77)

      CS: 66.7% (49.8-83.54)
      Compared with PS who had quit smoking for > 6 mo, CS were more likely to experience postoperative complications after onlay graft surgeries.

      Smoking cessation for > 6 mo can reduce complication risk to similar levels as those of NS.
      Mason 2009NS = 21%; defined as never smokers or smoked < 100 cigarettes in their lifetime

      PS =

      LQ = 5.1%; defined as persons who quit smoking for > 14 d to 1 mo pre-surgery

      IQ = 12%; defined as persons who quit 1-12 mo pre-surgery

      EQ = 50%; defined as persons who quit smoking > 12 mo pre-surgery

      CS = 20%; defined as smoking within 14 d pre-surgery
      799048.3Hospital mortality rate (OR and 95% CI)

      NS: 0.39%

      PS:

       LQ = 1.7% (4.6 [1.2-18])
      Versus NS.


       IQ = 1.3% (2.6 [0.65-11])
      Versus NS.


       EQ = 1.5% (2.5 [0.82-7.6])
      Versus NS.


      CS: 1.5% (3.5 [1.1-11])
      Versus NS.


      Pulmonary complications (OR and 95% CI)

      NS: 2.6

      PS:

       LQ = 6.2 (1.6 [0.85-3.1])
      Versus NS.


       IQ = 6.4 (1.5 [0.81-2.8])
      Versus NS.


       EQ = 5.8 (1.3 [0.77-2.2])
      Versus NS.


      CS = 6.9 (1.8 [1.05-3.1])
      Versus NS.
      Any smoking, past or current, was clearly associated with increased hospital mortality and pulmonary complications.

      Therefore, surgeons should counsel smokers that risk remains elevated regardless of timing of cessation, but that quitting holds a benefit that improves over time.

      Smoking seemed to have less of an effect on pulmonary complications compared with mortality. The longer the cessation period, the greater the risk reduction in pulmonary complications.

      During this study, the authors were unable to identify an optimal interval of smoking cessation.
      Myles 2002NS = 35%; defined as never smokers and with a COexp of ≤ 10 ppm

      PS = 24%; defined as patients who quit smoking for > 28 d pre-surgery

      CS = 41%; defined as CS or with COexp of > 10 ppm
      48938% Any respiratory complication and 95% CI

      NS: 25.9% (19.47-32.55)

      PS: 34.5% (25.83-43.13)

      CS: 33.5% (26.96-40.04)

      CS vs NS: (adjusted OR 1.71, 95% CI, 1.03-2.84)

      % wound infections and 95% CI

      NS: 0.6% (−0.55 to 1.71)

      PS: 2.6% (−0.3 to 5.48)

      CS: 3.7% (1.08-6.32)

      CS vs NS: (adjusted OR: 16.3, 95% CI, 1.58-1.75)
      Smokers (PS + CS) had a significantly increased risk of respiratory complication compared with NS.

      Adjusted OR 1.66 (95% CI, 1.07-2.57)
      Nakagawa 2001NS = 41%

      PS =

      RS = 5%; defined as patients who quit smoking 2-4 wk pre-surgery

      ES = 42%; defined as patients who quit smoking for > 4 wk pre-surgery

      CS = 13%; defined as patients who smoked within 2 wk pre-surgery
      28858% Overall incidence of postoperative pulmonary complications and 95% CI

      NS: 23.9% (16.2-31.66)

      PS:

       RS = 53.8% (26.75-80.95)

       ES = 34.7% (26.23-43.19)

      CS: 43.2% (27.28-59.2)

      Adjusted OR and 95% CI

      CS vs NS: 2.09 (0.83-5.25)

      RS vs NS: 2.44 (0.67-8.89)

      ES vs NS: 1.03 (0.47-2.26)
      For patients undergoing pulmonary surgery, smoking cessation of at least 4 wk pre-surgery can lower the risk of postoperative pulmonary complications.
      Padubidri 2001NS = 69%; defined as persons who had never smoked

      PS = 10%; defined as previous smokers who quit smoking ≥ 3 wk pre-surgery

      CS = 21%; defined as those who were still smoking at the time of surgery
      7480% Overall complication and 95% CI

      NS: 25.9% (22.14-29.7)

      PS: 25% (15.26-34.74)

      CS: 39.4% (31.66-47.04)

      % Mastectomy flap necrosis and 95% CI

      NS: 1.5% (0.49-2.61)

      PS: 2.6% (−0.97 to 6.23)

      CS: 7.7% (3.53-11.95)
      Patients who are scheduled to undergo breast reconstructions should quit smoking for at least 3 wk pre-surgery.

      Quitting in this time frame or earlier can lower the complications rate to that observed among NS.
      Sorenson 2005NS = 29%

      PS = 29%; defined as those who previously smoked but quit sometime pre-surgery

      CS = 42%; defined as those who smoked at time of surgery and at follow-up
      31045.5Association of smoking status with incisional hernia (adjusted OR and 95% CI)

      NS: 1

      PS: 1.57 (0.81-3.64)

      CS: 3.93 (1.82-8.49)
      CS are 4× at greater risk of incisional hernia than NS.
      Taber 2009NS = 63%; defined as never smokers

      PS = 18%; defined as those who previously smoked but quit at least 2 wk pre-surgery

      CS = 19%; defined as those who smoked up to the surgery day
      22145Mean hospital length of stay (days ±SD)

      NS: 2 ± 1

      PS: 2 ± 1

      CS: 2 ± 1

      % Postoperative infection and 95% CI

      NS: 3% (0.1-5.62)

      PS: 8% (−0.67-16.05)

      CS: 5% (−1.68-11.2)
      Among patients receiving laparoscopic donor nephrectomies, postoperative outcomes were similar among CS, PS who quit at least 2 wk pre-surgery, and NS.
      Vaporciyan 2002NS = 13%

      S =

      LQ = 23%; defined as persons who quit smoking < 1 mo pre-surgery

      EQ = 63%; defined as persons who quit smoking ≥ 1 mo pre-surgery
      25769.6% Incidence of major pulmonary events and 95% CI

      LQ: 21.7% (11.25-32.09)

      EQ: 9.2% (4.76-13.64)

      Risk of developing major pulmonary events (OR and 95% CI)

      LQ vs EQ = 2.70 (1.18-6.17)
      Timing of smoking cessation was a predictor of developing major pulmonary events.

      Smoking within 1 mo of pneumonectomy was strongly associated with the development of major pulmonary events.

      Patients who quit smoking late (ie, smoked within 1 mo pre-surgery) were 2.7× more likely to develop major pulmonary events compared with those who quit smoking for periods ≥ 1 mo.
      Warner 1984NS = 9%

      CS = 25%; defined as persons who never stopped smoking pre-surgery

      Stopped smoking < 2 wk pre-surgery = 17%

      Stopped smoking 2-4 wk pre-surgery = 9%

      Stopped smoking 4-8 wk pre-surgery = 6%

      Stopped smoking > 8 wk pre-surgery = 35%
      50077% Overall pulmonary problems (NS vs smokers) and 95% CI

      NS = 11.4% (1.98-20.74)

      Smokers: 39% (34.56-43.52)

      % Estimate of incidence of pulmonary complications and 95% CI

      NS = 11.4% (1.98-20.74)

      Stopped > 8 wk pre-surgery = 17% (11.45-22.55)

      Stopped 4-8 wk pre-surgery = 46% (27.54-64.46)

      Stopped 2-4 wk pre-surgery = 62% (47.66-76.34)

      Stopped < 2 wk pre-surgery = 57% (46.56-67.72) CS = 48.4% (39.59-57.19)
      Among patients undergoing coronary artery bypass grafting, clinical benefit due to smoking cessation was observed only in patients who quit smoking for > 8 wk pre-surgery. Smoking cessation in this period can lower the incidence of postoperative complications to levels comparable to those of NS.

      Preoperative smoking cessation for < 8 wk does not lower postoperative pulmonary complications.
      Warner 1989NS = 22%; defined as persons who never smoked and assigned a smoke-free day of 150

      PS = 69%; defined as previous smokers who quit smoking sometime in the past, and this group includes:

      LQ = 11%; defined as persons who quit smoking ≤ 8 wk pre-surgery

      EQ = 58%; defined as persons who quit smoking > 8 wk pre-surgery

      CS = 9%; defined as persons with cotinine levels > 0.5 μg/mL and assigned a smoke-free day of −1
      19283% Incidence of postoperative pulmonary complications and 95% CI

      NS: 11.9% (2.11-21.69)

      >6 mo: 11.1%

      EQ (>8 wk): 14.5% (7.88-20.94)

      LQ (≤8 wk): 57.1% (35.97-78.31)

      CS: 33% (11.55-55.11)
      Among patients undergoing coronary artery bypass grafting, smoking cessation < 2 mo pre-surgery does not seem to reduce the incidence of postoperative pulmonary complications below that observed in CS.

      Patients who quit smoking ≤ 2 mo pre-surgery were ∼4× more at risk of developing postoperative pulmonary complications (57.1% vs 14.5%).

      Smokers who quit > 6 mo pre-surgery had comparable complication rates as NS (11.1% vs 11.9%).
      Yamashita 2004NS = 48%; defined as persons who had never smoked

      PS = 37%; defined as smokers who quit smoking < 2 d pre-surgery

      CS = 16%; defined as smokers who smoked until 1 d pre-surgery
      100852.6% Intraoperative sputum volume increase and 95% CI

      NS: 9.4% (6.77-11.99)

      PS: 17.9% (13.98-21.8)

      CS: 18.2% (12.24-24.24)

      Smoke-free period and risk of intraoperative sputum volume increase (RR and 95% CI)

      Quit < 2 mo pre-surgery

      PS/CS vs NS: 2.0 (0.9-4.3)

      Quit < 2 wk pre-surgery

      PS/CS vs NS: 2.4 (1.2-4.8)

      % Total postoperative pulmonary complications and 95% CI

      NS: 1.7% (0.52-2.82)

      PS: 1.4% (0.18-2.54)

      CS: 1.9% (−0.23 to 4.01)
      In minor surgical patients undergoing general anesthesia, PS and CS were ∼2× more likely to have an increased intraoperative sputum volume than NS.

      Smoking cessation ≥ 2 mo pre-surgery can lower the risk of intraoperative sputum volume increase.
      AS = acute smoker; CG = control group; CI = confidence interval; CO = carbon monoxide; CS = current smoker; EQ = early quitters; ES = ex-smoker; HS = heavy smoker; IG = intervention group; IQ = intermediate quitters; LQ = late quitters; MS = mild smoker; N = sample size; NA = not applicable; NR = not reported; NS = nonsmoker; OR = odds ratio; ppd = packs per day; ppm = packs per month; PS = past smoker; PQ = past quitter; RR = relative risk; RS = recent smoker; SD = standard deviation; β = group numbers presented do not sum up to total N.
      low asterisk Definition requires classification according to studied groups.
      Versus NS.

      Risk of Pulmonary Complications

      Seven studies reported on the occurrence of pulmonary complications.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      • Yamashita S.
      • Yamaguchi H.
      • Sakaguchi M.
      • et al.
      Effect of smoking on intraoperative sputum and postoperative pulmonary complication in minor surgical patients.
      Data were available to test for differences from all trials. We found differences between past (pooled incidence 15%, 95% CI, 6-28) and current (20%, 95% CI, 8-26%) smokers, which indicated a statistically significant decrease in pulmonary complications (RR 0.81, 95% CI, 0.70-0.93, P = 0.003, I2 = 7%) for the former. There was no statistically significant difference between early and late quitters on this outcome (RR 0.88, 95% CI, 0.28-2.71, P = 0.81, I2 = 94%), possibly because of low power (9%).
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.

      Risk of Wound-Healing Complications

      Five studies provided data on wound healing.
      • Chang D.W.
      • Reece G.P.
      • Wang B.
      • et al.
      Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Myles P.S.
      • Iacono G.A.
      • Hunt J.O.
      • et al.
      Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.
      • Padubidri A.N.
      • Yetman R.
      • Browne E.
      • et al.
      Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      We found a statistically significant reduction in wound healing complications associated with former smokers compared with current smokers (RR 0.73, 95% CI, 0.61-0.87, P = .0006, I2 = 0%).

      Length of Hospital Stay

      Two studies reported on the average length of hospital stay.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.
      One study reported the mean duration of hospital stay as 8 days in past smokers and 9 days in current smokers.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      The other study found identical duration of stay after nephrectomy.
      • Taber D.J.
      • Ashcraft E.
      • Cattanach L.A.
      • et al.
      No difference between smokers, former smokers, or nonsmokers in the operative outcomes of laparoscopic donor nephrectomies.

      Mortality

      Only 2 studies reported on mortality.
      • Bluman L.G.
      • Mosca L.
      • Newman N.
      • Simon D.G.
      Preoperative smoking habits and postoperative pulmonary complications.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      Both studies had low event rates and found no difference between past and current smokers (RR 1.00, 95% CI, 0.64-1.55, P = .98).

      Duration of Cessation Period

      Seven studies provided adequate details on early versus late quitting and total complications.
      • Barrera R.
      • Shi W.
      • Amar D.
      • et al.
      Smoking and timing of cessation: impact on pulmonary complications after thoracotomy.
      • Kuri M.
      • Nakagawa M.
      • Tanaka H.
      • Hasuo S.
      • Kishi Y.
      Determination of the duration of preoperative smoking cessation to improve wound healing after head and neck surgery.
      • Mason D.P.
      • Subramanian S.
      • Nowicki E.R.
      • et al.
      Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study.
      • Nakagawa M.
      • Tanaka H.
      • Tsukuma H.
      • Kishi Y.
      Relationship between the duration of the preoperative smoke-free period and the incidence of postoperative pulmonary complications after pulmonary surgery.
      • Vaporciyan A.A.
      • Merriman K.W.
      • Ece F.
      • et al.
      Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation.
      • Warner M.A.
      • Divertie M.B.
      • Tinker J.H.
      Preoperative cessation of smoking and pulmonary complications in coronary artery bypass patients.
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      We found that shorter-term (<4 weeks) cessation compared with longer-term cessation (>4 weeks) resulted in a relative risk decrease of 20% (RR 0.80, 95% CI, 3-33, P = .02, I2 = 68%) in total complication rates. The residual heterogeneity found in this estimate is from Warner et al,
      • Warner M.A.
      • Offord K.P.
      • Warner M.E.
      • Lennon R.L.
      • Conover M.A.
      • Jansson-Schumacher U.
      Role of preoperative cessation of smoking and other factors in postoperative pulmonary complications: a blinded prospective study of coronary artery bypass patients.
      who reported only on early quitters (>8 weeks cessation) versus late quitters (≤8 weeks cessation) before surgery instead of > 4 weeks compared with < 4 weeks cessation. The removal of this study reduced the I2 value to 0%, but the effect size was no longer statistically significant (P = .52).

      Discussion

      Our review demonstrates a clear benefit of smoking cessation to prevent postoperative complications compared with continued smoking. We found that randomized trials that successfully introduced a smoking cessation intervention and attained abstinence had significantly decreased rates of complications. This effect was magnified with longer durations of cessation. This finding is in agreement with the evidence from observational studies that smoking cessation reduces total postoperative complications, pulmonary complications, and complications of wound healing. From our analyses of both randomized trials and observational studies, longer cessation periods provide greater reductions in clinical complications.
      There are both strengths and limitations to consider in our analysis. Strengths include our extensive searching, data abstraction in duplicate, and inclusion of both randomized and observational evidence that provides similar inferences. Our regression analysis shows that the length of time from smoking cessation is directly associated with the magnitude of subsequent complications. We found a larger treatment effect in randomized trials than in the observational studies. This may be due to the smaller sample size of the pooled randomized trials or may be a true therapeutic effect. The populations examined in the randomized trials were more homogenous than those in the cohort studies. Limitations of our analysis are predominantly related to the heterogeneous reporting of outcomes, inconsistent definitions of past smoking status, and differences in study designs across the observational studies. Although this has necessarily led to some study exclusions from the pooled analyses because of lack of relevant data on the key outcomes of interest, our observational study analyses indicated a significant decrease in complications for total, pulmonary, and wound healing complications. However, other analyses, such as those examining hospital stay and mortality, may be affected by low power. It is possible that if more trials reported specific outcomes, the results would be more precise.
      • Wetterslev J.
      • Thorlund K.
      • Brok J.
      • Gluud C.
      Trial sequential analysis may establish when firm evidence is reached in cumulative meta-analysis.
      Ours is not the first systematic review to examine smoking cessation with postsurgical outcomes. A meta-analysis by Thomsen et al
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      examined complication rates in 6 randomized trials and came to a similar effect estimate as that reported in our review. They also examined smoking cessation and demonstrated sustained cessation using a narrative review. Another narrative review by Theadom and Cropley
      • Theadom A.
      • Cropley M.
      Effects of preoperative smoking cessation on the incidence and risk of intraoperative and postoperative complications in adult smokers: a systematic review.
      included 12 observational studies examining postsurgical complications using inclusion criteria similar to ours. They did not pool studies but concluded that longer periods of cessation seem to be associated with decreased rates of complications. Our analysis includes 3 additional studies and pooled total complications to demonstrate that smoking cessation in observational studies is associated with a statistically significant reduction in total postsurgical complications, in accordance with the pooled randomized trials evidence, and significant reductions in pulmonary and wound-healing complications. Furthermore, our analysis demonstrated that increasing cessation periods results in a clinically important and statistically significant reduction in complications. The 2004 Surgeon General's Report on smoking concluded that there was sufficient evidence to infer a causal relationship between smoking and increased risks for adverse surgical outcomes related to wound healing and respiratory complications. However, the report relied on observational studies, did not examine the magnitude of risks or time periods of increased risk, and reported findings as a narrative review.

      The Health Consequences of Smoking: A Report of the Surgeon General. [Atlanta, Ga.]: Dept. of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health; Washington, DC: For sale by the Supt. of Docs., U.S. G.P.O.; 2004.

      A proof of concept randomized study by Sorensen et al
      • Sorensen L.T.
      • Karlsmark T.
      • Gottrup F.
      Abstinence from smoking reduces incisional wound infection: a randomized controlled trial.
      deliberately randomized smokers to receive an incision or not after several weeks of smoking cessation therapy. In an effort to determine the duration of cessation required, study subjects were evaluated at 1, 4, 8, and 12 weeks post-cessation, with incisions administered at each evaluation period. The largest and most sustained treatment effects were observed with 4 weeks cessation.
      The trials included in our randomized trials meta-analysis provided a variety of interventions that we classified as intensive or less intensive, ranging from the use of bupropion therapy and intensive counseling (intensive) to nicotine replacement therapy patch and brief counseling services (less intensive), as suggested by Thomsen et al.
      • Thomsen T.
      • Tonnesen H.
      • Moller A.M.
      Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation.
      More intensive interventions for cessation of smoking before surgery are therefore relevant for postoperative risk reduction. Pharmacotherapies available to surgery populations include nicotine replacement therapy, bupropion, and varenicline. A recent meta-analysis we conducted examined the short-term (∼4 weeks) cessation rates of these pharmacotherapies. Our study demonstrated consistent benefits from each intervention with varenicline, bupropion, and nicotine replacement therapy offering a cascade of relative benefit. The benefits of these short-term cessation interventions also seem to extend into longer periods of cessation (<6 months).
      • Wu P.
      • Wilson K.
      • Dimoulas P.
      • Mills E.J.
      Effectiveness of smoking cessation therapies: a systematic review and meta-analysis.
      • Mills E.J.
      • Wu P.
      • Spurden D.
      • Ebbert J.O.
      • Wilson K.
      Efficacy of pharmacotherapies for short-term smoking abstinance: a systematic review and meta-analysis.

      Conclusions

      In the United States, approximately 8 to 10 million procedures requiring surgery and anesthesia are performed on cigarette smokers.
      • Abidi N.A.
      • Dhawan S.
      • Gruen G.S.
      • Vogt M.T.
      • Conti S.F.
      Wound-healing risk factors after open reduction and internal fixation of calcaneal fractures.
      To interpret the possible impact of smoking cessation on population-wide complications, we conservatively estimate that, if all patients were offered a smoking-cessation intervention before surgery, and assuming a 25% cessation rate, this could result in 2 million (95% CI, 1,769,600-2,248,800) complications avoided, resulting in large savings for both patients and health services. The review finding that each additional week of smoking cessation has a significant impact on the reduction of postoperative complications highlights the importance of designing an appropriate secondary care smoking-cessation service. A service designed around early assessment of the smoking status of surgery patients and rapid referral to a smoking-cessation program could maximize the cessation period before surgery, resulting in greater reductions in postoperative complications in the secondary care setting.

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