3.15 The impact of smoking on treatment of disease

Last updated: March 2015
Suggested citation: Hurley, S, Greenhalgh, EM & Winstanley, MH. 3.15 The impact of smoking on treatment of disease. In Scollo, MM and Winstanley, MH [editors]. Tobacco in Australia: Facts and issues. Melbourne: Cancer Council Victoria; 2015. Available from http://www.tobaccoinaustralia.org.au/3-15-smoking-and-complications-in-medical-treatmen


3.15.1 Surgery

Smoking increases the risk of postoperative complications. Smokers' higher prevalence of chronic diseases, impaired pulmonary reserve, altered immune responses and impaired wound healing are thought to cause such complications. Poorer surgical outcomes result.1 Anaesthesia

The effectiveness of a number of commonly used anaesthetic drugs is reduced in smokers. Higher doses are therefore required. These drugs include opioids,2 neuromuscular blocking agents and some of the volatile agents that are administered by inhalation (via a mask or tracheal tube). The polycyclic aromatic hydrocarbons in cigarette smoke induce the liver enzymes that metabolise anaesthetics, at least partly accounting for these effects.3 Smoking does however decrease postoperative nausea and vomiting, possibly because of the increased metabolism of volatile anaesthetics.3

Smoking increases the risk of intraoperative and postoperative respiratory complications, including bronchospasm, aspiration, hypoventilation and hypoxaemia.4-6 An increased risk for smokers of admission to intensive care after general or orthopaedic surgery has been reported,4 and was attributed to smokers' higher perioperative pulmonary complication rate.

The Australian and New Zealand College of Anaesthetists recommends that patients who smoke be encouraged to quit at any time before surgery.7  The optimal timing of smoking cessation has been a source of controversy, though there is agreement that longer quitting is best.7 Research suggests that recent quitters are no worse off than continuing smokers in terms of pulmonary complications.  (see Section, 9 Postoperative complications

Smoking delays wound healing after surgery. Complications such as infection,10 dehiscence (bursting of sutures)11 and erosions (destruction of tissue surfaces) are increased.12, 13

Such smoking-associated complications are particularly problematic after plastic and reconstructive surgery, orthopaedic surgery (see Section 3.13.2), bowel surgery, dental surgery (see Section 3.11.4), microsurgery and organ transplantation.14–15

For example, after breast reconstruction, smoking has been associated with a doubling of the risk of complications (such as mastectomy flap necrosis or infection) and a five-fold increase in the risk of implant failure.17 Such poor surgical outcomes have led to a call for caution when undertaking breast reconstruction in smokers.18 Similarly, impaired wound healing and wound infection in smokers undergoing breast reduction surgery19, 20 have led to a suggestion that perioperative smoking cessation be an essential eligibility criterion for this surgery.20

Specific post-surgical complications linked with smoking include: a higher failure rate for oral mucosa graft urethroplasty;21 worse hearing and the need for repeat operations after ear surgery;22 increased complications post appendicectomy;23 increased mortality after liver transplantation;15 increased kidney transplant rejection;24 and poorer survival after heart transplantation if either the donor was, or the recipient is, a smoker.16, 25 The poorer organ transplantation outcomes in smokers, combined with the high demand for donated organs, have led to suggestions that smokers be given lower priority for organ transplants and debate about the ethics of such a policy.26-28

Smoking has also been implicated (in a report of four cases) as a risk factor for late-onset infection and other complications after facial injection of a filler substance for cosmetic purposes.29

The magnitude of the impact of smoking on perioperative outcomes was studied in a retrospective review of data from more than 500 000 patients in the US who had non-cardiac surgery.30, 31 Information on the 30-day period following surgery was compared for 82 304 current smokers and 82 304 control patients. Current smokers were 40% more likely to die than never smokers. Their risk of major morbidity also increased: the risk of pneumonia doubled, the risk of unplanned intubation almost doubled, and the odds of postoperative ventilation increased by 50%, cardiac arrest by 60%, myocardial infarction by 80%, and stroke by 70%. The risk of superficial and deep infections increased by 30% and 40%, respectively, and sepsis, organ space infections and septic shock were 30% to 50% more likely. The increased perioperative mortality and morbidity were confined to patients who had smoked more than 11 pack-years. Impact of smoking cessation

A meta-analysis published in 2011 reviewed data from randomised trials and observational studies that had compared postoperative complications in smokers and people who quit smoking before surgery. The analysis found that smoking cessation decreases postoperative complications. In the randomised trials, complications were reduced by about 40%. The review found that the longer the period of preoperative smoking cessation, the greater the reduction in complications.32

Another meta-analysis, also published in 2011, investigated the possibility that smoking cessation just before surgery may be harmful (see Section Data from nine studies that had studied the impact of quitting within eight weeks of surgery were combined. The analysis found no increase (or decrease) in overall postoperative complications in recent quitters compared with smokers. Although the study authors suggested that concern about possible adverse effects associated with stopping smoking just before surgery might therefore be unfounded, an accompanying 'Invited Commentary' pointed out that there was significant heterogeneity in the results of the studies that were combined, which was not surprising because some included patients who had quit two to three days before surgery whereas others included patients who had quit eight weeks prior to surgery.8 The commentators affirmed the wisdom of encouraging patients to quit smoking several months prior to surgery, but queried whether clinicians should be reassured that the timing of smoking cessation in anticipation of surgery is immaterial.

A systematic review published in 2012 explored the relationship between short-term preoperative smoking cessation and postoperative complications, and concluded that at least four weeks of abstinence from smoking reduces respiratory complications, and abstinence of at least three to four weeks reduces wound-healing complications. Short-term (less than four weeks) smoking cessation did not appear to increase or reduce the risk of postoperative respiratory complications.33 The Australian and New Zealand College of Anaesthetists recommend that, based on the current available evidence, anaesthetists and surgeons should not be dissuaded from advising patients to quit at any time before surgery.8

3.15.2 Drug interactions and effectiveness

Smoking alters the effects of a number of medications (see also Section on interactions with anaesthetics). Doctors and other healthcare workers need to be aware of these interactions when medications are prescribed and also when patients quit smoking, as drug dosages may need to be adjusted.34

Drug interactions fall into two categories: (i) pharmacokinetic interactions, which occur when cigarette smoke alters a drug's metabolism; or (ii) pharmacodynamic interactions, which occur when the physiological effects of cigarette smoke modify the physiological effects of the drug.35, 36

Pharmacokinetic interactions include increased metabolism of caffeine, heparin, warfarin, theophylline, a number of antipsychotic drugs and a number of benzodiazepines. A meta-analysis of the interaction between smoking and warfarin, for example, found that smoking increased warfarin dosage requirements by about 12%.37 Although it is difficult to know which of the estimated 4800 compounds in cigarette smoke cause these interactions, the polycyclic aromatic hydrocarbons are suspected. These hydrocarbons induce liver enzymes (see Chapter 13, Section and thereby hasten the clearance of any drug (or substance) whose metabolism requires the enzymes.35, 36

Pharmacodynamic interactions include: reduced response to corticosteroids in smokers who are asthmatic,39, 40 decreased sedation with benzodiazepines (possibly due to the stimulant effects of nicotine), slowed absorption of sub-cutaneous insulin (possibly due to reduced blood flow to the skin, mediated by nicotine), and an increased risk of cardiovascular adverse effects in women taking oral contraceptives.35, 36

In the above examples, smoking modifies the effects of particular drugs. It has also been hypothesised that bronchodilator drugs (mainly beta-2-agonists), prescribed for people with chronic obstructive pulmonary disease (COPD), may worsen the effects of cigarette smoke. The theory is that bronchodilation improves smoke inhalation, and may increase the deposition of cigarette smoke on the lungs, thereby increasing cardiovascular disease morbidity and mortality. This hypothesis is yet to be tested.41

3.15.3 Cardiovascular disease

As detailed in Section 3.1, smoking causes cardiovascular disease, and generally, if a person continues to smoke after developing cardiovascular disease their prognosis is worse than if they had quit.

For example, a study of more than 18 000 patients with coronary disease who were receiving a statin drug for coronary disease found that over a five-year period those who continued to smoke had about a 50% higher chance of a major cardiovascular event (death, myocardial infarction, stroke or cardiac arrest) than patients who quit.42 Similarly, poorer treatment outcomes have been reported for people who continue to smoke after coronary artery bypass grafting (CABG)43 or a diagnosis of heart failure,44 compared with people who quit.

3.15.4 Cancer

As detailed in Section 3.5, smoking causes numerous cancers. A review has concluded that overall survival is poorer in smokers with cancer. Studies of lung cancer, prostate cancer, cervical cancer, and head and neck cancer were cited.45 All these studies involved radiotherapy, leading to suggestions that radiotherapy is less effective in smokers. Higher irradiation complication rates for smokers in the studies covered by the review, and other studies,46, 47 support this suggestion. The review also found that the risk of secondary primary tumours is increased in smokers, for malignancies that are related to cancer and also for those that are not.45

The review found little information about the impact of smoking on chemotherapy for cancer, but suggested that treatment outcomes are likely to be worse because of the effects of cigarette smoke on immune function, appetite and basal metabolic rate.45

More severe pain has been associated with smoking in patients with cancer,48 and specifically for lung cancer49 and head and neck cancer.50 This may be because of the decreased effectiveness of opioids (due to induction of liver enzymes by components of cigarette smoke) described in Chapter 13, Section , and failure to increase the dose in response.

The 2014 Surgeon General’s report was the first in its series to review the associations between cigarette smoking and health outcomes in cancer patients and survivors. It concluded that smoking causes adverse health outcomes in people with cancer, while cessation improves their prognosis. Smoking increases all-cause mortality and cancer-specific mortality in cancer patients and survivors, and increases the risk for second primary cancers that are caused by cigarette smoking, such as lung cancer. Smoking is also associated with an increased risk of recurrence, poorer response to treatment, and increased treatment-related toxicity.51

A review of smoking cessation interventions in patients with cancer found that interventions increase quit rates but the difference was not statistically significant. Given the benefits of quitting on cancer outcomes, the authors called for research to identify more effective interventions for cancer patients.48

3.15.5 Treatment of infertility including assisted reproduction

As detailed in Section 3.6, women who smoke have reduced fertility and there is emerging evidence that fertility may also be reduced in male smokers. Smoking also has a negative impact on the outcomes of infertility treatment.53 In women participating in assisted reproduction programmes, a meta-analysis found that smoking is associated with lower pregnancy rates, higher chances of miscarriage and of ectopic pregnancy, and a lower probability of a live birth.54

One study found that for couples who smoked (either female, male or both), the risk of not achieving a pregnancy was about twice as high as for non-smokers.55 Female smoking during the period of infertility treatment has been associated with a decreased number of retrieved ova56 and a higher risk of repeated tubal ectopic pregnancies;57 male smoking has been associated with decreased live birth rates.56 Researchers have estimated that women who smoke need up to twice the number of in vitro fertilisation (IVF) cycles to conceive and suggest there is a correlation between the number of smoking years and the risk of not conceiving through IVF.53 Smoking cessation for both women and men is recommended for couples aiming to become pregnant58 and it has been suggested that access to fertility treatment should be conditional on quitting smoking.53

3.15.6 Contraception

As detailed in Section 3.1, smoking causes coronary heart disease, increasing the risk two- to four-fold.1 The 'combined' oral contraceptive pill (which contains the hormone oestrogen) also increases the risk of myocardial infarction two-fold.59 Women who both take the oral contraceptive pill and smoke have a 20-fold increase in the risk of coronary heart disease, compared with non-smokers who are not taking 'the pill'.60 The impact of smoking and the contraceptive pill is therefore 'synergistic', meaning that the risk of disease is multiplicative rather than additive. Heavier smokers have an even higher risk of coronary heart disease.61

Although the newer 'lower dose' versions of the pill may be associated with a lesser risk of developing coronary heart disease, risk is still elevated in smokers. There is insufficient evidence to evaluate the risk profile of the 'third-generation' pills (containing 30 μg or less of ethynyl estradiol and either gestodene or desogestrel) combined with smoking, but clinicians are advised to be wary when prescribing oral contraceptives to smokers aged in their mid-30s and to exercise extreme caution or avoid using them altogether in smokers aged over 40 years.61

In past decades the risk of stroke, particularly subarachnoid haemorrhage, has been significantly higher among smokers using the contraceptive pill. However research published since the 1990s following up women using lower dose pills is conflicting; some studies show increased risk, other studies have shown no significant effect.61

There is some evidence to suggest that the combined contraceptive pill has a higher failure rate in smokers than in non-smokers.60

3.15.7 Other conditions

A meta-analysis published in 2011 found that in patients receiving long-term haemodialysis or peritoneal dialysis, smoking increased the death rate (all-cause mortality) by 65%.62

Recent news and research

For recent news items and research on this topic, click here (Last updated March 2018)    


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22. Kaylie D, Bennett M, Davis B and Jackson C. Effects of smoking on otologic surgery outcomes. Laryngoscope 2009;119(7):1384-90. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19418530

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26. Bright R. Denial of hepatic transplantation on the basis of smoking: is it ethical? Current Opinion in Organ Transplantation 2010;15(2):49-53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20154621

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