Smoking and anaesthesia

Key points.

• •Smoking increases the risk of perioperative morbidity and mortality in a dose-dependent manner.
• •The Royal College of Anaesthetists advises that people who smoke should quit several weeks before surgery and should especially be encouraged not to smoke on the day of an operation.
• •There are more than 4500 chemicals in cigarette smoke, and the majority of these have detrimental effects on human body systems.
• •The preoperative assessment clinic provides an opportunity to discuss and encourage smoking cessation.
• •Electronic cigarettes are used by 2.3 million adults in the UK, but the long-term harm caused is unknown.

Learning objectives.

By reading this article, you should be able to:

• •Discuss the physiological effects of smoking.
• •Discuss the effects of smoking on perioperative morbidity and mortality.
• •Explain the rationale behind the timing of smoking cessation and how cessation may be achieved.

‘Smoking’ in this article describes the cigarette smoking of tobacco. The WHO has described tobacco as, ‘the only legal drug that kills many of its users when used exactly as intended by manufacturers’.¹ Smoking is the primary cause of preventable illness and premature death in the UK, accounting for almost 100,000 deaths per year and 6 million deaths per year worldwide. Although the prevalence of smoking in many countries is decreasing, in some areas of Africa and the Eastern Mediterranean it is rapidly increasing. By 2025, it is projected that across the world, there will be 1.1 billion people who smoke.² In 2013, the World Health Assembly, under a United Nations mandate, set a global voluntary tobacco target to help reduce and prevent premature and avoidable mortality from smoking. The agreed target is a 30% relative reduction in the prevalence of tobacco use.¹

Smoking carries a considerable burden of comorbidity and is estimated to cost the NHS around £2 billion each year. The NHS Five-Year Forward View states that ‘the sustainability of the NHS relies on a radical upgrade in disease prevention and public health’.³ This includes a reduction in smoking-related ill health. The joint briefing produced by Action on Smoking and Health (ASH), the Royal College of Anaesthetists (RCoA), the Royal College of Surgeons of Edinburgh, and the Faculty of Public Health provides advice and examples of good practice in relation to smoking and surgery.⁴

Quitting smoking before surgery leads to a reduced incidence of postoperative complications. The longer the period of cessation before surgery, the greater the benefit. The RCoA advises that people who smoke should quit smoking for at least several weeks before surgery and may benefit from abstaining on the day of surgery.⁴

History of smoking

Documented instances of tobacco smoking date from around 5000 BC when it was used by the Mayans during religious rituals. Smoking spread to Western civilisations in the 16th century after the colonisation of South America. It became more widespread during the First World War and reached peak prevalence in the UK after the Second World War.⁵ By 1949, 81% of men and 39% of women smoked regularly. Doll and Hill's⁶ reports in the 1950s of the adverse effects of smoking marked the beginning of a decline in its popularity. Earlier sceptics existed, however, including James I of England who in 1604 wrote in his ‘Counterblaste to Tobacco’ that ‘Smoking is a custom loathsome to the eye, hateful to the nose, harmful to the brain…and…dangerous to the lungs’.⁵

Constituents of cigarettes and cigarette smoke

Tobacco is prepared from the leaves of the tobacco plant through a curing process. The tobacco plant is part of the genus Nicotiana. More than 70 species of tobacco are known but the main commercial crop is N. tabacum. A more potent variant, N. rustica, may also be used.⁷ Components of a cigarette typically include tobacco rolled inside cigarette paper with a filter covered in a tipping paper through which to inhale. Cigarette smoke is a concentrated aerosol of liquid particles suspended in an atmosphere consisting mainly of nitrogen, oxygen, carbon monoxide, and carbon dioxide; it comprises a gaseous phase and a particulate phase. The particulate phase is defined as that which is eliminated on passing through a filter of pore size 0.1 μm. This is the Cambridge filter. This is a different entity to the filter tip of a cigarette described above which allows the passage of particles of much greater diameter.⁵

More than 4500 chemicals are present in cigarette smoke, and many of these have adverse effects on human body systems. The main component of the gaseous phase is carbon monoxide and of the particulate phase, nicotine.

Carbon monoxide

Carbon monoxide is the main component of the gaseous phase of cigarette smoke and its presence adversely affects oxygen delivery to the tissues. The inhalation of carbon monoxide leads to increased formation of carboxyhaemoglobin, COHb. In people who smoke, the percentage of COHb in arterial blood is 2–12%, compared with <1.5% in non-smokers. A greater percentage of COHb significantly reduces the capacity of haemoglobin to bind and carry oxygen. Carbon monoxide has around a 300-fold greater affinity for haemoglobin than the affinity of oxygen for haemoglobin, and therefore the formation of COHb is favoured over the formation of oxyhaemoglobin.⁸ Because of its much greater affinity for haemoglobin, the COHb dissociation curve is shifted to the left of the oxyhaemoglobin dissociation curve (Fig. 1). P₅₀ is the partial pressure of oxygen (PO₂) at which the haemoglobin saturation is 50% under standard conditions; the P₅₀ of the COHb dissociation curve is greatly reduced in comparison with the P₅₀ of the oxyhaemoglobin dissociation curve, which adversely affects oxygen delivery. The dissolved oxygen content is unchanged, but this represents a small contribution only to blood oxygen content.

Fig 1.

The P₅₀ of the COHb dissociation curve is reduced in comparison with that of the oxyhaemoglobin dissociation curve, that is the affinity of carbon monoxide for haemoglobin is far greater than the affinity of oxygen for haemoglobin.

In addition, COHb adversely affects oxygen delivery to the tissues through its effect on the oxyhaemoglobin dissociation curve. The presence of COHb causes a left shift (i.e. a reduction in P₅₀) of the oxyhaemoglobin dissociation curve partly because of a reduction in 2,3-di-phosphoglycerate (2,3-DPG) levels. This reduces the ability to unload oxygen in the tissues.

For these reasons, hypoxaemia occurs when one breathes air in the presence of supranormal levels of COHb, and a patient who smokes has reduced physiological reserve to maintain their PO₂ at times of physiological stress. Although many arterial blood gas analysers provide a percentage for COHb, most oxygen saturation measurement devices are unable to distinguish oxyhaemoglobin from COHb and give an erroneously high value for oxygen saturation in the presence of significant levels of COHb.

Nicotine

Nicotine is the main component of the particulate phase of cigarette smoke. Tobacco leaves contain many different alkaloids, of which nicotine is the most prevalent. Nicotine content varies depending on where the nicotine leaf is attached to the tobacco plant and the blend used by different tobacco companies. Nicotine is addictive in humans; the chemical structure of nicotine is similar to that of acetylcholine and so plays a role in cerebral neurotransmission.

A typical cigarette contains around 2 mg nicotine. This is readily absorbed across the alveolar membrane. Nicotine crosses the blood–brain barrier and enters the cerebral circulation within 20 s. It stimulates nicotinic acetylcholine receptors and through a variety of second messengers, stimulates the secretion of neurotransmitters such as noradrenaline, adrenaline, vasopressin, serotonin, dopamine, and β-endorphin. Nicotine increases cardiac output and the risk of tachydysrhythmias. At increasing doses the stimulant effects of nicotine diminish; high doses have a sedative and depressant effect. Nicotine has a half-life of 30 min and is metabolised by the cytochrome P450 enzyme system (mainly via CYP2A6 and CYP2B6) to a number of different metabolites, including cotinine, an active metabolite, which remains in the bloodstream for up to 20 h.6, 9

Additional chemicals

The classes of other chemical constituents of tobacco smoke and their effects are shown in Table 1.

Table 1.

Classification of chemical constituents of cigarette smoke

Chemical group	Examples	Common biological effects
Polycyclic hydrocarbons	Naphthalene, fluorene, phenanthrene	Respiratory tract inflammation and liver dysfunction
Nitrosamines	Nicotine-derived nitrosamine ketone (NNK)	A procarcinogen and immunosuppressant via tumour necrosis factor-α and interleukin modulation
Aza-arenes	Quinolene	Hepatic carcinogen demonstrated in animal studies
Aromatic amines	Toluidine, anisidine	Bladder carcinogen
Ammonia		Corrosive to mucous membranes at high levels; respiratory tract inflammation
Pyridine		Headache; dizziness; amnesia; irritant to eyes, nose, throat, and skin
Other gases	Butadiene, acrolein, isoprene, benzene	Carcinogens

Tar

The nicotine-free remainder of the particulate phase of cigarette smoke is known as ‘tar’. The chemical components in tar and their toxicity vary widely across tobacco from different sources. Measurement of tar is therefore a crude measure of the relative toxic potential of tobacco combustion products. Tar yields of cigarette brands are measured using a standardised method involving a smoking machine. On the basis of these results, cigarette brands have been classified as high, medium, or low yield cigarettes. However, a criticism is that the smoking machine does not accurately simulate human smoking and also that smokers have ways of increasing their intake, for example by blocking ventilation holes and taking deeper or more frequent puffs.¹⁰

Relevant clinical effects of cigarette smoke

Cardiovascular

Smoking is the largest preventable cause of cardiovascular morbidity and mortality. The effects are well documented and widely appreciated by anaesthetists. Smoking is associated with a three-to four-fold increase in coronary heart disease. The sympathomimetic effects of nicotine and the reduction in oxyhaemoglobin caused by carbon monoxide adversely affect oxygen supply and demand to the myocardium. An increased incidence of cardiac dysrhythmias with arterial blood COHb values as low as 4–5% has been described. Smoking causes adverse effects on an individual's lipid profile, endothelial injury, and the development of atherosclerotic plaques. Smoking is an independent risk factor in the development of peripheral vascular disease, thromboembolic disease, and stroke. A strong positive dose-dependent correlation exists between smoking and subarachnoid haemorrhage, and the association appears to be greater amongst women than amongst men. The risk reduces in a dose-dependent manner with smoking cessation.¹

Respiratory

Smoking is the cause of 90% of lung cancers. Around 20% of smokers develop chronic obstructive pulmonary disease. This is characterised by a small airway obstruction and a reduction in forced expiratory volume in 1 s (FEV₁), and may be associated with emphysematous and bullous changes to lung tissue.¹² Smoking causes an acute reduction in airway diameter as a bronchoconstrictive reflex to inhaled particles. Premature small airway closure occurring during expiration results in an increase in closing volume and altered ventilation/perfusion relationships. Smoking is associated with hypersensitive airway reflexes. An increased incidence of adverse events perioperatively—for example cough, breath holding, and laryngospasm—is seen. Mucus production and viscosity are increased, whereas mucus clearance is impaired through damage to ciliary structure and function.¹³ This promotes sputum retention and increases the risk of developing pneumonia and respiratory failure.

Gastro-intestinal

Smoking causes relaxation of the lower gastro-oesophageal sphincter and an increased incidence of gastro-oesophageal reflux disease and peptic ulcer disease. There appears to be a reduced rate of postoperative nausea and vomiting amongst smokers possibly because of increased metabolism of volatile agents by CYP2E1.⁹ Smoking is associated with an increased incidence of Crohn's disease and a reduced incidence of ulcerative colitis.¹¹

Other systems

Cigarette smoking inhibits immune function, and this results in poorer wound healing and increased wound infection rates. Patients who smoke have abnormal bone metabolism, and fracture healing may be delayed.

Involuntary or passive smoking

The effects of smoking are not limited to smokers themselves. The WHO defines passive smoking as ‘exposure to second-hand tobacco smoke, which is a mixture of exhaled mainstream smoke and side stream smoke released from a smouldering cigarette and diluted with ambient air’. Involuntary smoking involves inhaling carcinogens and other toxic components that are present in second-hand tobacco smoke.¹⁴

Pharmacological effects of smoking

Nicotine and polycyclic aromatic hydrocarbons induce the cytochrome p450 system, particularly CYP1A1, CYP1A2, and CYP2E1. The metabolism of many drugs is altered including that of theophylline, caffeine, haloperidol, propranolol, and volatile agents. Greater postoperative opioid requirements are described consistently amongst patients who smoke although the mechanism for this is poorly understood. It is not simply because of the increased metabolism of substrates, and additional factors (e.g. altered pain thresholds and receptor-mediated effects) are likely to have a role.⁹ Chronic nicotine use may have an effect on the number and sensitivity of nicotinic acetylcholine receptors at the postsynaptic membrane. A number of small studies investigating the potentially altered pharmacodynamic effects of neuromuscular blocking agents have shown inconsistent results, and there is currently no clear evidence that patients who smoke require altered dosing of these drugs.⁹

Perioperative complications associated with smoking

Intraoperative complications

A study of a little more than 26,000 patients of whom 26% were patients who smoke found an increased incidence of all specific respiratory adverse events in the group who smoked.¹⁵ The respiratory events investigated included reintubation after planned extubation, laryngospasm, bronchospasm, aspiration, hypoventilation and hypoxaemia, and pulmonary oedema. Those at the greatest risk of the adverse events were younger patients who smoke (aged 16–39 yr) and those who were obese. The relative risk of developing one of the above complications was 1.8 across all smokers, 2.3 in the younger population, and 6.3 in young, obese patients who smoke. The relative risk of perioperative bronchospasm was found to be 25.7 in younger patients who smoked and who also had chronic bronchitis.

Postoperative complications

Recent meta-analyses have demonstrated that people who smoke have increased postoperative mortality and an increased rate of all cardiac, pulmonary, and septic complications (see Table 2 for details). In addition, there is a clear dose–response relationship between amount smoked and morbidity—that is morbidity is increased in smokers in a dose-dependent manner.¹⁶ Current smokers (defined as those having smoked in the preceding year compared with never-smokers) are 1.38 times more likely to die within 30 days (95% confidence interval, 1.11–1.72). The findings regarding morbidity are consistent with previous studies on patients undergoing cardiac, vascular, thoracic, general, urology, orthopaedic, and plastic reconstructive surgery. In general surgery, smoking is an independent risk factor for anastomotic breakdown. Preoperative smoking has also been shown to be associated with an increased risk of admission to the ICU, emergency readmission to hospital, and longer inpatient postoperative stays.¹³ By quantifying the increased likelihood of 30-day mortality and highlighting the broad range of serious possible smoking-related complications, the clinician's ability to motivate smoking cessation in patients scheduled for elective surgery may be improved.

Table 2.

Adverse effects of smoking on postoperative 30-day morbidity

Morbidity	Odds ratio (95% confidence interval)
Pneumonia	2.09 (1.80–2.43)
Unplanned intubation	1.87 (1.58–2.21)
Mechanical ventilation	1.53 (1.31–1.79)
Cardiac arrest	1.57 (1.10–2.25)
Myocardial infarction	1.80 (1.11–2.92)
Stroke	1.73 (1.18–2.53)
Superficial wound infection	1.30 (1.20–1.42)
Deep wound infection	1.42 (1.21–1.68)
Organ space infection	1.38 (1.20–1.60)
Septic shock	1.55 (1.29–1.87)

Smoking cessation

Perioperative timing of smoking cessation

Stopping smoking before surgery reduces the risk of postoperative complications. Evidence varies as to the optimum time to quit. Studies of patients undergoing cardiac surgery in the 1980s suggested that quitting within 8 weeks of surgery led to increased pulmonary complications. However, a more recent meta-analysis found no increase in complications amongst smokers who quit within 2 months of surgery.¹⁷ Trials of at least 4 weeks smoking cessation had a significantly larger treatment effect in terms of the perioperative morbidity and mortality than shorter trials—that is, the longer the period of cessation before surgery, the better.

It is likely that even a brief period of smoking cessation may confer some benefit, given the acute effects of nicotine and carbon monoxide on the cardiovascular system. As the half-life of carbon monoxide is 4 h when breathing air and the half-life of nicotine is 30 min, even a relatively short period of abstinence from smoking helps to avoid some of the adverse effects.

It is not clear whether smoking cessation within a few hours or days reduces perioperative complications, but there is no clear evidence of harm either, and smoking cessation should be encouraged at any time.

Effects of smoking cessation

After quitting, the symptoms of cough and wheeze decrease within weeks. Mucociliary clearance starts to improve after a week but lung inflammation takes much longer to subside. Goblet cell hyperplasia regresses and alveolar macrophages decrease, but alveolar destruction, smooth muscle hyperplasia, and fibrosis may be permanent.¹⁸ Smoking cessation decreases all-cause mortality in patients with coronary artery disease by approximately one third. It is estimated that it takes several months for this risk to decrease after the patient has quit smoking. The risk of coronary heart disease and cerebrovascular disease approaches the risk of never-smokers within 10–15 yr.¹⁹ The rate of decline of FEV₁ amongst smokers increases as FEV₁ becomes worse. However, the younger the patient at the time of quitting, the slower the rate of decline, eventually approaching the rate in never-smokers.¹² Smoking cessation reduces mortality rates, with the largest benefit being in those who quit under the age of 30 yr, but even those who quit at 60 yr of age are likely to have survival benefit of up to 3 yr.²⁰

Smoking cessation advice and programmes

Guidance from the National Institute of Health and Care Excellence recommends that when patients who smoke access secondary care services, they should be identified and offered intensive support to quit.²¹ Patients who smoke are more likely to quit if they are offered a combination of interventions, with combined behavioural support and pharmacotherapy. Healthcare professionals should be trained to give brief advice on stopping smoking and should have contact with the local NHS Stop Smoking Service to which they can refer. If patients do not wish to attend the service, they should be offered brief advice and support to help them quit, and pharmacotherapy as appropriate.

Use of the Very Brief Advice (VBA) tool is encouraged. This comprises a three-step approach: ask, advise, and act.⁴

• •‘Ask’ and record smoking history. Smoking history is typically reported in ‘pack-years’ where the number of packs of cigarettes smoked per day is multiplied by the number of years the person has smoked (e.g. 1 pack-year represents smoking 20 cigarettes per day for 1 yr).
• •‘Advise’ that the most effective way to quit is with a combination of medication and specialist support.
• •‘Act’ on the patient response. Give information, refer, and prescribe.

Brief advice offered by a physician has been shown to increase quit rates.²² Trials using preoperative intensive smoking cessation interventions found a 10-fold relative risk of smoking cessation compared with usual care. Studies looking at brief interventions found a smaller effect of smoking cessation rates although quit rates were high in the control groups, likely reflecting the fact that people who smoke have a high motivation to quit ahead of major surgery.²³ This ‘teachable moment’ should be used to good effect.⁴

Pharmacological options

Three drugs are licensed in the UK for the support of smoking cessation and have proven efficacy.²⁴

• •Nicotine replacement therapy; available as patches or in shorter acting forms, for example lozenges, chewing gum, or nasal sprays.
• •Oral bupropion; a nicotinic receptor antagonist with dopaminergic and adrenergic actions; it may work by blocking the effects of nicotine, relieving withdrawal or reducing depressed mood.
• •Oral varenicline; a nicotinic receptor partial agonist that binds less effectively than nicotine.

Electronic cigarettes

There has been an increase in recent years in the popularity of electronic cigarettes (e-cigarettes), or ‘vaping’. They are currently used by 2.3 million adults in the UK. E-cigarettes use a battery to heat a solvent and disperse an aerosol that contains nicotine, water, and sometimes flavouring. Nicotine can therefore be delivered to the respiratory tract without combustion.

The potentially harmful effects of vaping are an area of interest. Current opinion is that e-cigarettes are likely to be less harmful than cigarettes, but studies have found the aerosol to contain heavy metals, polycyclic hydrocarbons, nitrosamines, volatile organic compounds, and inorganic compounds.²⁵

It is clear that e-cigarettes help some people to quit smoking, although no randomised controlled trials have been carried out to compare the effectiveness of e-cigarette use with more established pharmacotherapy to promote and maintain smoking cessation.

Declaration of interest

The authors declare that they have no conflicts of interest.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Biographies

Michael Carrick FRCA is a specialty registrar in anaesthesia at the Leeds Teaching Hospitals NHS Trust.

Jonathan Robson MRCP (Resp) is a consultant in respiratory and general medicine at St James's University Hospital, Leeds, whose special interests include lung cancer, pleural disease, and interventional pulmonology.

Caroline Thomas BSc (Hons), FRCA is a consultant in anaesthesia at St James's University Hospital, Leeds, whose special interests include perioperative medicine and anaesthesia for thoracic and colorectal surgery.

Matrix codes: 1A01, 1A02, 2A03, 3A01