It has been estimated that at least one third (and probably closer to one half) of all patients presenting for surgery are smokers, which predisposes them to significant postoperative respiratory complications. As such, patients are usually counseled to stop smoking before surgery and may even be prescribed a nicotine patch as therapy.

Certainly, a few patients achieve the recommended goal of smoking cessation 4 to 6 weeks before surgery, but by far the greater number do not manage to stop smoking until the day before or even the morning of surgery (“No, I don’t smoke, I quit two hours ago”). Acute smoking cessation has the paradoxic action of transiently increasing airway secretions due to improved mucociliary transport, but the balance of effects on the pulmonary and cardiovascular systems is beneficial. These include a decrease in blood carbon monoxide levels as well as a rightward shift in the oxygen-hemoglobin dissociation curve and an increase in tissue oxygenation. However, anesthesia providers must be aware of the unintended consequences of smoking cessation—balanced against the obvious benefits is the fact that the polycyclic aromatic hydrocarbons in smoked tobacco act as strong inducers of the P450 1A2 enzyme, moderate inducers of P450 2E1, and inducers of some not yet well characterized phase II enzymes. Abrupt cessation of smoking may cause alterations in the blood levels and/or end organ effects of various medications, possibly in ways that could produce inconvenience or even harm to patients.

Only smoked tobacco acts as an enzymatic inducer. Rather, it is the polycyclic aromatic hydrocarbons that must be smoked in order to induce metabolic enzymes. The P450 1A2 enzyme catalyzes the metabolism of a number of substrates that are of clinical relevance in the perioperative period. These include cyclobenzaprine, flecainide, propranolol, theophylline, and R-warfarin (Table 43.1). In the days following smoking cessation, the decreased availability of P450 1A2 decreases the metabolic clearance of these 1A2 substrates, leading to significantly increased blood levels. These increases in substrate levels can produce frank toxicity (such as with theophylline) and otherwise complicate perioperative management. There have been cases of increased bleeding attributable to smoking cessation in patients who
take warfarin. The effects of smoking cessation may be mimicked by the abrupt introduction of inhibitors of P450 1A2, such as caffeine, cimetidine, ethinylestradiol, and many of the fluoroquinolones (Table 43.1). Other inducers of 1A2 (besides tobacco smoking) include carbamazepine, rifampin, and modafinil (Table 43.1).