Anesthetic considerations in smokers: A scoping review

Abstract

Tobacco smoking is a well-established modifiable risk factor that significantly influences perioperative outcomes through complex physiological and pharmacological mechanisms. Despite widespread awareness of its long-term health consequences, a considerable proportion of surgical patients continue to smoke at the time of their procedures. The objective of this review is to synthesize current evidence regarding the impact of smoking on anesthetic management. Smoking induces chronic inflammation and structural changes in the respiratory tract, which may increase the risk of intraoperative hypoxemia, bronchospasm, and postoperative pulmonary complications. Cardiovascular risks are similarly elevated due to smoking-related endothelial dysfunction, increased sympathetic activity, and impaired myocardial oxygen balance. Moreover, nicotine and other components of tobacco smoke alter drug metabolism, particularly via hepatic enzyme induction, affecting the pharmacokinetics of commonly used anesthetics and analgesics. Smokers also exhibit altered pain perception and increased opioid requirements postoperatively, complicating analgesic strategies. In conclusion, an in-depth understanding of the multifaceted effects of smoking on anesthetic care is essential for optimizing outcomes and reducing perioperative morbidity in this high-risk group.

Introduction

Tobacco smoking remains one of the most prevalent modifiable risk factors affecting global health, contributing to over 8 million deaths annually.[1] Despite increasing public health efforts to curb tobacco use, a significant proportion of surgical patients are current or former smokers.[2] The anesthetic management of this population is particularly challenging due to the complex physiological and pharmacological changes induced by smoking. These changes have implications for both general and regional anesthesia, as well as perioperative outcomes.[3]

Smoking significantly impacts the respiratory and cardiovascular systems, making it highly relevant perioperatively. It causes airway inflammation, mucus hypersecretion, and impaired mucociliary clearance, elevating the risk of bronchospasm and postoperative pulmonary complications.[4] Elevated carboxyhemoglobin levels in smokers can impair oxygen delivery and complicate monitoring.[5] Nicotine-induced sympathetic stimulation, vasoconstriction, and endothelial dysfunction may also lead to hemodynamic instability during anesthesia.[6] Additionally, smoking induces hepatic enzymes, accelerating anesthetic metabolism and possibly requiring higher doses.[7] Smokers may also be less sensitive to opioids and sedatives, necessitating cautious dose titration.[8]

Importantly, smoking is associated with worse perioperative outcomes, including higher rates of wound infection, delayed healing, and increased mortality. These risks are not limited to chronic heavy smokers; even light or occasional smokers demonstrate increased perioperative morbidity.[9] Evidence suggests that preoperative smoking cessation can significantly reduce complications and improve outcomes, yet many patients continue smoking up to the day of surgery.[10]

Given the growing emphasis on patient safety and enhanced recovery protocols, understanding the specific anesthetic requirements and challenges in smokers is critical. This review aims to provide an overview of the current evidence on anesthetic requirements in smokers, with a focus on clinical implications, pharmacological considerations, and perioperative management strategies.

Pathophysiological changes in smokers relevant to anesthesia

Cigarette smoking induces several pathophysiological alterations that significantly impact anesthetic management. These changes include respiratory, cardiovascular, metabolic, and immunological systems, necessitating careful consideration during the perioperative period.

Respiratory system alterations: Chronic exposure to cigarette smoke leads to inflammation of the airway epithelium, resulting in increased mucus production, impaired mucociliary clearance, and structural remodeling of the airways.[11,12] These changes contribute to airflow obstruction and increased airway resistance, predisposing smokers to intraoperative bronchospasm and postoperative pulmonary complications.[12,13] Additionally, smoking can cause pulmonary edema and atelectasis due to increased vascular permeability and inflammatory mediator release.[12,14] Ventilation-perfusion mismatching is also observed, leading to hypoxemia and reduced tissue oxygen delivery.[15]

Cardiovascular effects: Nicotine and other constituents of cigarette smoke stimulate the sympathetic nervous system, resulting in increased heart rate, blood pressure, and systemic vascular resistance.[6,16] These hemodynamic changes can complicate anesthetic induction and maintenance, particularly in patients with underlying cardiovascular disease. Moreover, smoking-induced endothelial dysfunction impairs vasodilation and promotes a prothrombotic state, increasing the risk of perioperative cardiovascular events.[6,17]

Metabolic and pharmacokinetic considerations: Smoking induces hepatic cytochrome P450 enzymes, particularly CYP1A2, leading to altered metabolism of various anesthetic agents, including propofol and opioids.[7] This enzymatic induction may necessitate adjustments in drug dosing to achieve the desired anesthetic effects. Furthermore, chronic smoking is associated with increased oxidative stress and mitochondrial dysfunction, which can impair tissue oxygen utilization and exacerbate perioperative metabolic disturbances.[8]

Immunological impairments: Cigarette smoke compromises immune function by impairing alveolar macrophage activity and reducing the efficacy of neutrophil responses. These immunosuppressive effects increase susceptibility to postoperative infections, including pneumonia and surgical site infections. Additionally, smoking delays wound healing by impairing fibroblast function and collagen synthesis, which further complicates postoperative recovery.[18,19]

Preoperative assessment in smokers

Effective preoperative evaluation in smokers is essential to mitigate perioperative complications and guide individualized anesthetic planning. The evaluation begins with a detailed smoking history, including duration, intensity (pack-years), current status, and time since cessation if applicable. This information informs risk stratification and aids in estimating the potential benefits of preoperative smoking cessation.[10,20]

Pulmonary function assessment is central to evaluating operative risk in smokers. Chronic tobacco exposure contributes to airway hyperreactivity, reduced mucociliary clearance, and obstructive lung disease.[11] Spirometry is recommended for individuals with a history of chronic obstructive pulmonary disease or unexplained dyspnea, with forced expiratory volume in 1 second providing objective indices of pulmonary function. In patients with moderate-to-severe disease, additional testing such as arterial blood gas analysis or diffusion capacity of the lungs for carbon monoxide may be warranted. Furthermore, chest imaging may help identify structural abnormalities, including emphysematous changes or undiagnosed malignancies.[21,22]

Cardiovascular assessment is equally critical, as smoking contributes to hypertension, coronary artery disease, and peripheral vascular disease.[23] Smokers undergoing major surgery should be evaluated for cardiac risk factors per guidelines, such as those by the American College of Cardiology/American Heart Association.[24] Electrocardiography and, when indicated, stress testing or echocardiography may uncover occult ischemia or left ventricular dysfunction.[24]

Preoperative evaluation should also include a thorough review of current medications, with consideration of potential drug interactions or altered pharmacokinetics that may affect perioperative management. Additionally, nutritional status and signs of chronic systemic inflammation, which are more prevalent in smokers, should be reviewed due to their implications for wound healing and infection risk.[25]

Anesthetic drug interactions and pharmacokinetics in smokers

Tobacco smoking induces a multitude of pharmacokinetic alterations that significantly affect the metabolism, distribution, and clearance of anesthetic agents. These effects are primarily mediated by the induction of hepatic cytochrome P450 enzymes, which metabolize a wide range of anesthetic and adjunctive drugs.[26] Chronic exposure to polycyclic aromatic hydrocarbons in tobacco smoke upregulates these enzymes, thereby enhancing the hepatic clearance of certain medications, potentially leading to subtherapeutic plasma levels during anesthesia.[27]

More clinically relevant are agents such as ropivacaine and lidocaine, whose hepatic clearance may be increased in chronic smokers, potentially reducing their efficacy during regional anesthesia.[28,29] Smoking also influences the pharmacodynamics of inhalational anesthetics. Studies suggest that smokers may require higher concentrations of desflurane and sevoflurane to achieve the same minimum alveolar concentration due to altered pulmonary function and receptor desensitization.[30] Moreover, the uptake of inhaled anesthetics is affected by smoking-induced airway inflammation and increased mucus production, which may modify the speed and uniformity of anesthetic gas exchange.[26]

Intravenous agents such as propofol may also be influenced by smoking. Although the data are less consistent, some reports suggest increased clearance of propofol in chronic smokers, necessitating higher infusion rates to maintain desired plasma concentrations.[31] Similarly, opioid metabolism, particularly for agents such as fentanyl and remifentanil, can be altered, although clinical implications remain somewhat variable.[32]

Importantly, nicotine itself, whether from cigarettes, nicotine replacement therapy, or electronic cigarettes, has sympathomimetic properties that can interact with anesthetic agents. Nicotine-induced vasoconstriction and elevated catecholamine levels may blunt the hemodynamic effects of induction agents and necessitate tailored anesthetic plans.[33]

Overall, anesthetic drug management in smokers requires a thorough understanding of altered pharmacokinetics and pharmacodynamics. Personalized dosing strategies, close intraoperative monitoring, and consideration of alternative agents may be necessary to ensure both efficacy and safety.

Pain perception and analgesic requirements in smokers

Tobacco smoking is associated with significant alterations in pain perception and analgesic requirements due to complex neurophysiological, pharmacological, and inflammatory changes induced by chronic nicotine exposure. While nicotine has acute analgesic effects mediated through the activation of nicotinic acetylcholine receptors and downstream modulation of dopaminergic and endogenous opioid pathways, chronic exposure leads to paradoxical hyperalgesia, likely due to receptor desensitization, neuroadaptation, and a pro-inflammatory state.[34] Jamner et al.[35] demonstrated that smokers who used nicotine gum exhibited greater tolerance to cold pressor-induced pain compared to those who received placebo gum, indicating an acute analgesic effect of nicotine. Notably, smoking history did not influence pain responses, suggesting that the observed hypoalgesia was due to the direct antinociceptive properties of nicotine rather than relief from acute withdrawal symptoms. Furthermore, nicotine administration did not affect mood or task performance, implying that its analgesic effect was independent of any mood-altering properties. These findings were later confirmed by Girdler et al.,[36] who found that smokers had greater thresholds and tolerance to cold pressor pain than nonsmokers. Conversely, evidence suggests that smokers may use tobacco as a coping mechanism for managing pain, which may heighten the urge to smoke, as assessed through self-reported cravings and observed smoking behavior. In a randomized study involving 132 smokers, laboratory-induced cold pressor pain significantly increased self-reported urges to smoke and led to a shorter time before initiating smoking. Notably, the link between pain and smoking motivation was partially mediated by pain-induced negative effects.[37]

However, in contrast, chronic smokers often report higher pain levels and increased pain sensitivity. Utilizing the Collaborative Health Outcomes Information Registry of 8584 patients attending the Stanford Pain Management Center, Khan and colleagues demonstrated that smokers reported significantly higher levels of pain intensity, pain interference, pain behaviors, reduced physical functioning, greater fatigue, more pronounced sleep-related impairment and disturbance, increased anger, lower emotional support, and elevated symptoms of depression and anxiety compared to nonsmokers. Longitudinal mixed-model analyses further revealed that smokers consistently exhibited worse outcomes over time, particularly in pain interference, fatigue, sleep-related problems, anger, emotional support, and depression.[38] A meta-analysis suggested that smoking was associated with increased axial neck pain after cervical spine surgery.[39] In a study involving 160 men who underwent lumbar puncture before anterior cruciate ligament reconstruction, cigarette smoking was associated with increased postoperative pain intensity, shown by delayed pain perception, higher pain visual analog scale scores, and lower beta-endorphin and higher substance P levels in the cerebrospinal fluid of active smokers.[40]

Clinical studies consistently demonstrate increased analgesic requirements among smokers. In a study involving 407 men who underwent in-hospital surgery, current smokers required more opioid analgesics during the first 72 hours following surgery compared to non-smokers and former smokers. They also reported higher pain intensity when moving and at rest on day 1 after surgery.[41] Similarly, in a retrospective review of 236 male patients who received intravenous patient-controlled analgesia after distal gastrectomy with gastroduodenostomy, opioid consumption by smokers was higher than that of nonsmokers.[42] In a study involving 90 patients who underwent the standard total intravenous anesthesia, the total consumption of propofol was significantly higher in current smokers than in passive and never smokers, and in passive smokers than in never smokers.[43] Another study, including 77 patients who underwent lower extremity orthopedic surgery under regional anesthesia, found that the duration of sensory blockade was significantly longer in the smoking group than in the non-smoking group.[44] In a study involving 248 patients who underwent total hip arthroplasty, opioid consumption in both the immediate postoperative and 90-day postoperative periods was significantly higher among smokers than nonsmokers.[45] In a retrospective analysis of 89 patients who underwent coronary artery bypass graft, smokers deprived of nicotine required a larger dose of opiates in the first 48 hours after operation than did nonsmokers.[46]

Collectively, the evidence indicates that smokers not only experience more severe pain but also exhibit reduced responsiveness to standard analgesics. This necessitates individualized, multimodal pain management strategies and close perioperative monitoring to optimize outcomes in this high-risk population.

Smoking cessation before surgery

Smoking cessation prior to surgery plays a crucial role in optimizing perioperative outcomes, particularly in smokers who are at higher risk of respiratory, cardiovascular, and wound healing complications.[10,47] The optimal timing for smoking cessation before surgery remains a topic of debate, with evidence suggesting that even short-term cessation can yield significant benefits. Research indicates that smoking cessation for at least 4–8 weeks before surgery provides the most substantial reduction in postoperative complications. This window allows for the reversal of many of the detrimental effects of smoking on the cardiovascular and respiratory systems. Smoking-induced impairment in mucociliary clearance and increased airway reactivity can persist for up to 8 weeks following cessation, resulting in a significant reduction in postoperative pulmonary complications such as pneumonia and atelectasis.[48] Furthermore, smoking cessation improves oxygenation and pulmonary function,[49] which is essential for anesthetic management, particularly with the use of volatile anesthetics and neuromuscular blocking agents.[10] From a cardiovascular perspective, smoking accelerates the development of atherosclerosis and endothelial dysfunction, increasing the likelihood of perioperative cardiovascular events.[17,50] The benefits of smoking cessation on vascular tone and endothelial function can be seen within weeks, with studies showing that cardiovascular morbidity and mortality decrease significantly after 4 weeks of cessation.[17,50] Moreover, cessation before surgery reduces sympathetic tone and heart rate variability, leading to more stable hemodynamics during the perioperative period.[17,50,51]

In cases where a patient cannot quit smoking in time, strategies such as nicotine replacement therapies can be employed. These therapies help mitigate withdrawal symptoms and reduce the cravings for nicotine, facilitating a smoother perioperative course.[52,53] Therefore, the timing of smoking cessation must be integrated with pharmacological strategies to optimize both cessation and anesthesia outcomes.

Conclusion

Smoking has profound effects on anesthesia practice, ranging from altered pharmacokinetics to increased perioperative risks and complex pain management needs. Preoperative identification of smoking status, patient counseling, and individualized anesthetic planning are essential to improve surgical outcomes. Further research is needed to clarify the mechanisms underlying chronic pain in smokers and to optimize anesthetic protocols for this high-risk group.

Institutional review board statement

Not applicable.

Informed consent statement

Not applicable.

Data availability statement

We did not generate new data.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.