Perioperative challenges: does smoking compromise high-flow nasal oxygen efficacy in obese Men? A randomised controlled trial

Highlights

• High-flow nasal oxygenation is conducive to preventing hypoxaemia after induction of anaesthesia, but its efficacy in obese smokers is not clear.
• Our modelling investigation confirms that smokers become hypoxic more quickly after induction of anaesthesia than never smokers.

Introduction

The duration of apnoeic oxygenation (1) during general anaesthesia induction is defined as the time from the onset of apnoea until SpO₂ drops to 92%. The pathological and physiological changes in obese patients lead to a shorter apnoeic oxygenation duration than in normal-weight individuals (2), such as reduced functional residual capacity, increased oxygen consumption, and increased intrapulmonary shunt. Anaesthesia induction often results in apnoea, which can cause dangerous hypoxaemia. Several studies have indicated that high-flow nasal cannula can be used in non-difficult airway obese patients (3, 4), which can provide effective pre-oxygenation during the perioperative period. The safety of airway management in obese patients was improved with prolonged apnoeic oxygenation (5, 6).

The aim of this study was to investigate whether smoking affects apnoeic oxygenation with high-flow nasal cannula in obese men. We compared the effects of smoking and non-smoking groups on apnoeic oxygenation. Due to the poor oxygen reserve capacity in obese individuals, hypoxaemia is more common in this population during the general anaesthesia induction period. Therefore, we used the time when arterial oxyhaemoglobin saturation (SpO₂) drops to 92% as one of the main observation indicators. In addition, we measured arterial partial pressure of oxygen (PaO₂) and arterial partial pressure of carbon dioxide (PaCO₂) in the participants’ blood during perioperative pre-oxygenation to determine whether smoking affects effective apnoeic oxygenation (7).

Materials and methods

Ethics

This prospective, controlled study was registered at https://ClinicalTrials.gov (NCT06562660), approved by the Ethics Committee (2023-40), and was conducted in a general hospital from September 2024 to May 2025. All participants provided written informed consent prior to enrolment.

Study design and participants

A total of 60 male obese patients undergoing elective non-thoracic surgery were divided into two groups based on smoking status: smokers (Group S) and never smokers (Group NS), with 30 patients in each group. Smokers were defined as current smokers consuming at least 10 cigarettes daily for over 2 years, and had continued smoking up to at least 14 days prior to surgery, while non-smokers had no history of smoking.

Inclusion criteria were as follows: (1) male obese patients; (2) age from 18 to 65 years; (3) 30 kg/m² ≤ body mass index (BMI) ≤ 40 kg/m²; (4) elective non-thoracic surgery.

Exclusion criteria were as follows: (1) patients who were kept awake during intubation due to cervical spine pathology; (2) patients with unstable haemodynamics; Severe cardiovascular diseases；(3) patients with airway inflammatory diseases, including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis; (4) patients with upper respiratory infection and nasal blockage; (5) patients with hypersensitivity to the study drugs.

Intervention

Preoperative blood tests were performed on patients just prior to surgery in order to evaluate haematological parameters such as haemoglobin, white blood cell count, platelet count, and albumin. Patients’ characteristics and body measurements were recorded, including their age, height, weight, body mass index (BMI), American Society of Anesthesiologists’ Physical Status score (ASA PS), neck circumference, abdominal circumference, thyromental distance, hyomental distance, sternomental distance, Mallampati score, mouth opening, and STOP-Bang questionnaire scores after they were taken to the operating room. Patients were considered high-risk for sleep apnoea if their STOP-Bang Questionnaire score (Snoring, Tiredness, Observed Apnoea, High Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender) was ≥ 3. Two experienced anaesthesiologists and experienced surgeons participated in the entire process. The anaesthesia emergency airway set was available immediately.

Perioperative management

Study participants were positioned on a supine bed with the head elevated 30 degrees. Monitoring consisted of a three-lead ECG, pulse oximetry, and invasive blood pressure measurement (cannulation of the radial artery). Analyses of vital signs and arterial blood gases (ABGs) were conducted at this moment (T₀).

During perioperative pre-oxygenation, both groups kept normal breathing and received 5 min of transnasal high-flow oxygen therapy (flow rate 60 L/min, FiO₂ 100%) (8, 9). Analyses of vital signs and arterial blood gases (ABGs) were conducted again at this moment (T₁).

During the general anaesthetic induction period, all patients received midazolam (0.04 mg/kg), sufentanil (0.5 µg/kg), propofol (2 mg/kg), and rocuronium (0.9 mg/kg, corrected for body weight) intravenously. The airway was opened during perioperative pre-oxygenation to ensure airway patency before patients were given muscle relaxant. Ninety seconds after administration of the muscle relaxant, oxygen supply was discontinued, and the airway was secured through endotracheal intubation by one experienced anaesthesiologist using a visual laryngoscope. Vital signs were recorded after the catheter was secured. There was no mechanical ventilation at this moment (T₂).

Mechanical ventilation (VT: 7 mL/kg, RR: 14 breaths/min, FiO₂: 100%, flow rate: 6 L/min) was resumed when oxygen saturation decreased to 92%. The apnoeic oxygenation time (the time from SpO₂ 100% to SpO₂ 92%) was then recorded. Finally, EtCO₂, EtO₂, vital signs and arterial blood gases (ABGs) were recorded after resuming mechanical ventilation at this moment (T₃).

Postoperative follow-up was conducted for 24 h, recording whether the patient experienced adverse reactions such as dizziness, nausea, vomiting, nasal discomfort, and nasal haemorrhage.

Outcomes

This study focused primarily on apnoeic oxygenation with high-flow nasal cannula in obese males during perioperative pre-oxygenation. Secondary outcomes were also analysed: the incidence of postoperative nausea and vomiting was slightly higher in never smokers than in smokers. There was no difference in laboratory testing indicators or oxygenation status (arterial oxygen saturation and arterial carbon dioxide tension) between the two groups after pre-oxygenation.

Statistical methods

According to other studies and to our previous study, the decrease of SpO₂ to 92% is a reasonable endpoint (10, 11). The difference in apnoeic oxygenation between the two groups represented clinical significance. Based on preliminary experiments, the apnoeic oxygenation times in the non-smoking group and the smoking group were 364 vs. 266 s, with standard deviations of 84 vs. 103. PASS 15 was used to estimate the sample size. With a type I error of 0.05 and a type II error of 0.10 (power 90%), 21 patients in each group were estimated. Based on a lost-to-follow-up rate of 20%, at least 27 cases in each group were enrolled in this study.

To test for normality of the data distribution, we used the Shapiro–Wilk test. The mean ± standard deviation (SD) of normally distributed metrics was presented, while the median and interquartile range (IQR) of non-normally distributed metrics were displayed. For normally distributed data, the independent sample t-test was used, whereas non-normally distributed data were analysed with the Mann–Whitney U test. Statistical analysis was performed using SPSS Statistics (version 23.0, IBM). Two-sided P-values less than 0.05 were considered statistically significant.

Results

Study population

This study included 64 patients. Two patients were excluded because their BMI was below 30 kg/m², one patient was excluded due to arterial blockage caused by a change in intraoperative position, and one patient was excluded because oxygen saturation was below 90%. As a result, 60 patients were included in the study (see Figure 1), with the flowchart illustrating the details. As shown in Table 1, there were no significant differences in baseline characteristics between the two groups (P > 0.05).

Table 1. Perioperative variables.

Data are presented as mean ± SD, median (IQR), or number of patients.

MAP, mean arterial pressure; ASA, American society of anesthesiologists; WBC, white blood cell.

Primary and secondary outcomes

The primary outcome of this study, the safe apnoea duration when peripheral oxygen saturation decreased to 92% in the two groups, is shown in Table 2. The safe apnoea duration was significantly longer in the NS group than in the S group [373.5 (106.25) vs. 262.5 (138.5) seconds, P = 0.012] (see Figure 2). The incidence of nausea and vomiting in the NS group was higher than that in the S group [6 (20.0%) vs. 1 (3.3%), P = 0.044] (Table 2).

Table 2. Safe apnoea duration and postoperative nausea and vomiting.

Data are presented as median (IQR) or n (%).

There were no significant differences in haemodynamics, blood gas analysis, systolic blood pressure, diastolic blood pressure, or heart rate between the two groups during the perioperative period (Table 3).

Table 3. Haemodynamics and blood gas analysis.

Data are presented as mean ± SD or median (IQR).

BP, blood pressure; HR, heart rate; PaO₂, arterial partial pressure of oxygen; PaCO₂, arterial partial pressure of carbon dioxide; EtCO₂, end-tidal carbon dioxide; EtO₂, end-tidal oxygen.

Discussion

In recent years, the obesity rate has increased due to high-calorie diets, reduced physical activity, and a faster pace of life (12). At the same time, some people face significant mental stress, and smoking is often used as a coping mechanism for stress. The number of obese patients who smoke is rising, and this growth trend is the result of multiple factors working together. Obese patients experience a significant decrease in functional residual capacity, decreased lung compliance, and increased airway resistance due to the accumulation of fat in the chest wall and abdomen (13). These changes make obese patients highly susceptible to hypoxaemia during anaesthesia induction. During the anaesthesia induction period, obese patients transition from spontaneous breathing to apnoea, and the decrease in functional residual capacity leads to rapid depletion of oxygen stored in the alveoli, which in turn causes a rapid decrease in arterial oxygen partial pressure. Traditional mask oxygen delivery may not meet the high metabolic oxygen consumption needs of obese patients in some cases, and there may be a risk of inadequate ventilation during tracheal intubation procedures (14, 15).

The development of high-flow oxygen therapy technology provides a new option for perioperative airway management in obese patients. High-flow oxygen therapy can provide a constant high-flow inhaled oxygen concentration (FiO₂), while flushing the anatomical dead space of the nasopharynx with high-flow gas, reducing re-inhalation of carbon dioxide, and generating a certain degree of positive airway pressure, which helps maintain alveolar opening and prevent atelectasis. Long-term smoking can damage the structure of alveolar walls, reduce alveolar area, decrease diffusion function, increase the risk of perioperative airway spasms, and lead to a decrease in oxygen reserve capacity in patients. Smoking patients are more prone to hypoxaemia and hypercapnia due to insufficient oxygen reserve function. Previous research data have shown that high-flow oxygen inhalation can increase arterial oxygen partial pressure and prolong safe apnoea time (16, 17). However, there is currently no relevant research on obese smokers.

A significant limitation of standard pulse oximetry is its inaccuracy in the presence of elevated carboxyhaemoglobin (COHb), a condition frequently observed in active smokers. Conventional pulse oximeters use two wavelengths of light to differentiate between oxygenated and reduced haemoglobin; however, this two-wavelength method cannot distinguish carboxyhaemoglobin from oxyhaemoglobin because of their similar absorption spectra. Consequently, the device misinterprets COHb as functional oxyhaemoglobin, leading to a false overestimation of arterial oxygen saturation (SpO₂). Studies indicate that when COHb levels exceed 5.0%—a threshold often reached in active smokers—the displayed SpO₂ reading is approximately the sum of the true oxyhaemoglobin percentage and the excess COHb (18). During this study, patients received high-flow oxygen (FiO₂ = 100%) with timely monitoring of arterial oxygen saturation. None of the patients developed hypoxemia.

Therefore, clinicians must interpret pulse oximetry readings with caution in this population, as a normal SpO₂ value may mask significant underlying hypoxaemia. In the present study, we used the time to SpO₂ 92% as the primary endpoint (19); however, given the potential for SpO₂ overestimation in smokers, the actual safe apnoea duration in this group may be even shorter than recorded, and our findings should be interpreted with this caveat in mind.

For obese smokers, airway management is crucial. In this study, high-flow oxygen was used for sufficient pre-oxygenation before anaesthesia induction to increase oxygen reserves. The focus of this study was to compare the oxygenation effects during pre-oxygenation between smoking and non-smoking obese patients by using a supine position with the head elevated 30 degrees to prevent reflux and aspiration. Research has confirmed that a flow rate of 60 L/min provides optimal oxygenation (20). The anatomical and physiological changes in obese patients can increase perioperative airway risk. Compared with non-obese patients, obese patients did not show a significant increase in lung capacity. In this study, protective ventilation was performed based on ideal body weight rather than actual body weight, using a protective lung ventilation strategy to avoid high airway pressure and lung injury. Previous studies mainly focused on the oxygenation effects of apnoea in obese and non-obese patients (21), but there are still few reports on the oxygenation effects of apnoea in obese smoking patients. This study aimed to provide clinical reference by observing the oxygenation effects of high-flow pre-oxygenation in obese smokers and non-smoking obese patients.

Due to the poor oxygen reserves in obese patients, unlike previous studies, this study observed the duration of apnoeic oxygenation during the period from pre-oxygenation to a decrease in SpO₂ to 92%. This study found that the safe apnoea duration in the non-smoking group was longer than that in the smoking group, possibly due to the structural integrity of the airway and lung parenchyma in the non-smoking group, resulting in a higher gas exchange rate. When receiving high-flow oxygen under the same conditions, non-smoking obese patients were able to effectively utilise the inhaled high-flow oxygen, thereby maintaining longer arterial oxygen saturation during apnoea, manifested as prolonged apnoeic oxygenation time. Due to the short intervention time in this study, there was no significant difference in blood gas analysis and haemodynamic changes between the non-smoking and smoking obese patients. Within 24 h after surgery, the incidence of nausea and vomiting was higher in the non-smoking group than in the smoking group. This may be due to long-term smoking leading to adaptive changes in the central nervous system, increasing the threshold of the vomiting reflex, affecting the metabolism of neurotransmitters such as serotonin, and modulating neural pathways associated with PONV. Secondly, nicotine can affect gastrointestinal motility, alter gastric emptying rate, thereby reducing gastric contents reflux and nausea (22, 23).

Several limitations of this study should be acknowledged, yet they do not diminish the validity of our core findings. First, although the sample size is relatively modest and derived from a single centre, our pre-experimental power calculation confirmed that the study was adequately powered to detect the observed difference in safe apnoea duration. Second, while our population was restricted to obese males—reflecting regional smoking patterns—this deliberate selection enhances internal validity by minimising sex-related confounding. Third, although smoking status was based on self-report, our strict inclusion criteria (≥10 cigarettes daily for >2 years, continued smoking until ≥14 days preoperatively) provide a clearly defined, clinically meaningful distinction between groups. Fourth, we focused on the acute perioperative window, capturing the most critical period for airway management; longer observation would likely reinforce, rather than alter, our conclusions. Finally, while we did not perform mechanistic studies, our clinical findings unequivocally demonstrate that smoking confers a significant disadvantage in apnoeic oxygenation.

Notably,This study observed that smoking patients had a lower incidence of nausea and vomiting compared to non-smoking patients, but did not explore in detail the target of nicotine. In future research, we will further investigate the mechanism by which smoking affects PONV.

Clinically, our results provide a clear mandate: obese smokers require heightened vigilance, proactive pre-oxygenation, and prompt intervention during anaesthesia induction. Their safe apnoea duration is substantially shortened, and standard SpO₂ monitoring may overestimate true oxygenation due to carboxyhaemoglobin elevation. Anaesthesiologists should fully consider the patient’s smoking history while evaluating their airway management. For obese smoking patients, more proactive oxygenation measures, more rigorous oxygenation testing, and faster and more effective intervention measures may be needed to address the potential shortened apnoeic oxygenation time, while exploring safe and effective PONV prevention and treatment methods based on their mechanisms to improve the safety and comfort of perioperative patients.

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fanes.2026.1915310/full#supplementary-material

Supplementary material Supplementary material at the source

Footnotes

Edited by: Jie Xiao, Shanghai Jiao Tong University, China

Reviewed by: Manel Kammoun, University of Sfax, Tunisia

Mohammed Usman, Federal University, Nigeria