Clinical evaluation of non-intubated spontaneous ventilation video-assisted thoracoscopic surgery in patients with non-small cell lung cancer and compromised pulmonary function: a propensity score-matched analysis

Introduction

Background

As human life expectancy increases, the number of elderly patients diagnosed with lung cancer has steadily increased (1). Video-assisted thoracoscopic surgery (VATS) remains the preferred first-line treatment for patients undergoing curative intervention. However, concomitant respiratory diseases and compromised pulmonary function are frequently observed in this population. During one-lung ventilation (OLV) using double-lumen endotracheal intubation, there is an increased risk of ventilator-induced lung injury, which may lead to severe cardiorespiratory complications (2,3). Consequently, certain non-elderly patients with impaired pulmonary function—including those with chronic obstructive pulmonary disease, emphysema, or interstitial pneumonia, as well as those requiring contralateral reoperation following unilateral lobectomy—are often precluded from surgical treatment due to their inability to tolerate OLV (4).

With the widespread adoption of the enhanced recovery after surgery (ERAS) concept, the anesthesia technique of maintaining spontaneous breathing without tracheal intubation—termed “tubeless” anesthesia or non-intubated spontaneous ventilation video-assisted thoracoscopic surgery (NIVATS)—has been increasingly implemented in clinical practice. Accumulating evidence indicates that NIVATS, when combined with VATS for lung resection, demonstrates favorable safety and efficacy. This approach significantly reduces airway trauma associated with intubation, barotrauma associated with OLV, and adverse events related to anesthetic agents (e.g., sedatives and opioids), including postoperative nausea and vomiting, delayed emergence, and residual neuromuscular blockade. As a result, NIVATS may facilitate faster postoperative recovery (5-7). However, due to potential intraoperative risks—including persistent hypoxemia, hypercapnia, and hemodynamic instability caused by mediastinal shift—the precise clinical benefits and optimal indications of NIVATS remain subjects of ongoing debate (8,9).

Study objective

Research on the application of tubeless anesthesia in non-small cell lung cancer (NSCLC) patients with compromised pulmonary function is limited. To address this gap in the literature, we conducted a propensity score-matched study to evaluate the feasibility and safety of tubeless VATS in this high-risk cohort. Our findings may expand the surgical criteria for lung resection in patients with limited pulmonary reserve. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1637/rc).

Methods

This clinical study was conducted at Anyang Tumor Hospital, and approved by its Institutional Ethics Board (No. 2025KY05H01). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and applicable clinical practice guidelines. Informed consent was obtained from all patients enrolled in the study.

Participants

This study consecutively recruited 162 patients who underwent single-incision thoracoscopic radical resection for lung cancer between January 2021 and May 2025. The main inclusion criteria were as follows: American Society of Anesthesiologists (ASA) physical status I–III, and the presence of compromised pulmonary function as defined by the Chinese Expert Consensus on the Diagnostic Criteria of Adult Pulmonary Function (10) and the Global Initiative for Chronic Obstructive Lung Disease diagnostic criteria (11).

The inclusion criteria were as follows:

• Pulmonary functional criteria [patients with compromised pulmonary function were required to meet criterion i (mandatory) plus criterion either ii or iii]: (i) exercise capacity: a 6-minute walking distance <400 m or a stair-climbing height <22 m; (ii) post-bronchodilator forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ≤70%; (iii) FEV₁ ≤1.6 L;
• Pathologically confirmed NSCLC;
• Tumor diameter ≤4 cm;
• Eastern Cooperative Oncology Group performance status ≤1;
• Absence of severe arrhythmias (e.g., atrial fibrillation or frequent premature ventricular contractions);
• Absence of severe cardiac insufficiency.

The exclusion criteria were as follows:

• Hemodynamic instability;
• Partial pressure of carbon dioxide in arterial blood (PaCO₂) ≥50 mmHg after pulmonary rehabilitation;
• Dense pleural adhesions;
• Clinical stage N2 disease;
• ASA physical status ≥ IV;
• Expected operative time >3 hours;
• Contraindications to epidural anesthesia (e.g., coagulopathy or spinal deformity);
• Intraoperative conversion from non-intubated to intubated anesthesia.

Anesthesia and surgical procedures

All patients underwent thoracoscopic surgery under a non-intubated anesthetic regimen using a dual‑port approach. In the NIVATS group, patients received a target-controlled infusion of propofol (2–4 µg/mL) and remifentanil (1–3 ng/mL), along with intravenous dexmedetomidine (0.5–1 µg/kg/h). The depth of anesthesia was maintained with a bispectral index value between 40 and 60. A laryngeal mask airway (LMA) was inserted on loss of consciousness, and end-tidal carbon dioxide partial pressure (PETCO₂) was continuously monitored using capnography. The remaining patients received epidural anesthesia via catheter placement at the T6–T7 or T7–T8 interspace. Anesthesia was maintained with 0.375% ropivacaine, with the sensory block level adjusted to between the second and tenth intercostal nerves.

All patients received standard intraoperative monitoring; however, PETCO₂ monitoring was not performed in those receiving epidural anesthesia. Arterial catheterization was employed for continuous blood pressure monitoring and arterial blood gas analysis when peripheral capillary oxygen saturation (SpO₂) was ≤93%. Central venous catheterization was performed based on the specific surgical requirements and patient condition. During the operation, oxygen was administered at a flow rate of 3–5 L/min with an fraction of inspired oxygen (FiO₂) of 100%.

Following the completion of the main surgical procedures—defined as resection of the lung lesion, lymph node dissection, and pleural lavage—synchronous intermittent mandatory ventilation was initiated to facilitate carbon dioxide elimination. Dopamine or norepinephrine was administered to maintain a mean arterial pressure >60 mmHg. After surgery, patients were transferred to the post-anesthesia care unit for removal of the LMA or epidural catheter. All patients received self-controlled intravenous analgesia postoperatively and were subsequently transferred to either the intensive care unit or general ward based on their clinical condition.

In the VATS group, a Mallinckrodt double-lumen endobronchial tube was inserted with the assistance of cisatracurium, followed by the initiation of OLV. A protective ventilation strategy was employed to maintain adequate oxygenation, consisting of low tidal volumes (5–6 mL/kg) and an extended expiratory phase.

Surgical procedure

The thoracoscopic procedures were similar in the NIVATS and VATS groups, which followed the consensus guidelines of the American Association for Thoracic Surgery. The patient was placed in a full lateral decubitus position. The surgical procedure for each patient was determined according to the stage and location of the lesion in computed tomography images. Anatomical resection included radical resection of lung cancer and segmental resection; non-anatomical resection included lung wedge resection, bullae resection, and lung volume reduction surgery.

Outcomes measures

The primary outcomes were complications associated with anesthesia, duration of surgery, duration of anesthesia, and post-operative pulmonary complications. The secondary outcomes included intraoperative blood loss volume, anesthesia emergence time, and the time to first ambulation after surgery.

Statistical analysis

Continuous data were assessed for normality using the Shapiro-Wilk test and expressed as mean ± standard deviation or median (interquartile range). Categorical variables were presented as number (%). Numerical variables were analyzed using the independent samples t-test or the Mann-Whitney U test. Categorical variables were compared using Pearson’s Chi-squared test or Fisher’s exact test. Generalized linear models were used to compare the intensity of postoperative sore throat (POST) between groups NIVATS and VATS.

Univariate logistic regression analysis was performed to identify the predictors of POST, and odds ratios with 95% confidence intervals were calculated. Variables with P<0.1 in the univariate analysis were incorporated into a subsequent multivariate adjusted ordinal logistic regression analysis. A P value <0.05 was considered statistically significant.

The statistical analyses were performed using IBM SPSS Statistics (version 23.0, IBM Corp, Armonk, NY, USA) and R package (version 4.3.1) software.

Results

In total, 162 patients were screened from January 2021 to May 2025. Of these patients, 38 did not meet the inclusion criteria, and 124 refused to participate in this study. Ultimately, 124 patients were assigned to the NIVATS group (n=62) or the VATS group (n=62) (Figure 1).

Figure 1 The study flowchart. NIVATS, non-intubated spontaneous ventilation video-assisted thoracoscopic surgery; VATS, video-assisted thoracoscopic surgery.

Prior to matching, statistically significant differences were observed between the two groups in terms of the FEV₁, surgical approach and pathologic tumor-node-metastasis (TNM) staging. A 1:1 propensity score matching (caliper =0.25, standardized mean difference <0.1) was then performed based on the following baseline variables: gender, age, body mass index (BMI), ASA physical status classification, surgical approach, and TNM staging.

Following matching, 62 patients were included in both the non-intubated and intubated groups. After matching, no statistically significant differences were observed between the two groups in terms of gender, age, smoking history, BMI, ASA score, cardiopulmonary comorbidities, pathological type, surgical approach, or TNM staging. However, FEV₁ remained significantly lower in the non-intubated group. This reflects our deliberate inclusion of patients with compromised lung function in this cohort (Table 1).

Perioperative anesthetic and surgical rehabilitation-related indicators

After propensity score matching, no significant differences were observed between the NIVATS and VATS groups in terms of the operative time, anesthesia duration, or cardiovascular complications. However, NIVATS was associated with significantly better outcomes across multiple intraoperative and postoperative parameters, including a lower incidence of intraoperative hypoxemia, shorter anesthesia emergence time, earlier time to first ambulation, reduced postoperative hospital stay, less throat discomfort, higher patient-reported satisfaction, and fewer pulmonary complications (all P<0.05). Notably, the NIVATS group had a higher incidence of hypercapnia compared with the VATS group (Table 2).

Analysis of perioperative complications

In relation to the intraoperative complications, the incidence of hypoxemia necessitating intervention was 17.7% in the NIVATS group, significantly lower than the 38.7% observed in the VATS group. Conversely, the incidence of hypercapnia necessitating intervention was 33.9% in the NIVATS group, significantly higher than the 17.7% observed in the VATS group. Moreover, the incidence of tracheal intubation-related complications (including hoarseness and pharyngeal pain) and pulmonary complications was also significantly reduced in the NIVATS group compared to the VATS group. Although the NIVATS group had a lower overall incidence of cardiovascular complications than the VATS group, the difference was not statistically significant (Table 3).

Discussion

Surgery is the first-line strategy for radical resection in patients with early-stage (stage I) lung cancer and compromised pulmonary function. Even with partial lobectomy (e.g., wedge resection or segmentectomy), a resection margin ≥2 cm may achieve therapeutic outcomes comparable to those of radical resection. Compared with non-surgical treatments, surgical intervention significantly improves long-term patient prognosis (12,13). However, in patients with poor pulmonary function, tracheal intubation and OLV are associated with a high incidence of anesthesia-related complications, including ventilator-induced barotrauma, airway injury, hypoxemia due to ventilation-perfusion (V/Q) mismatch, and lung ischemia-reperfusion injury (14,15). Current evidence indicates that “tubeless” anesthesia—combining epidural anesthesia with intrathoracic vagal nerve block and supplemental sedation—preserves spontaneous respiration while maintaining adequate surgical conditions. This approach significantly reduces anesthesia-related adverse events, cardiopulmonary complications, and postoperative stress responses (8,15). Despite significantly lower baseline FEV₁ in the non-intubated group (both pre- and post-PSM), these patients achieved comparable or superior perioperative outcomes versus the intubated cohort, underscoring the benefit of non-intubated techniques in high-risk populations.

While the principal risks of non-intubated anesthesia are hypoxemia and hypercapnia (8,16,17), secondary concerns include hemorrhage (5), mediastinal flutter (9), and hemodynamic instability (5,15). Despite these risks, our study demonstrated a lower incidence of hypoxemia requiring intervention in the NIVATS group, although all patients received an FiO₂ of 1.0 [intervention is warranted for SpO₂ <92% (>1 min) or PaO₂ <60 mmHg]. This finding may be explained by the physiological advantages of spontaneous breathing: active thoracic expansion helps preserve alveolar patency and promotes more effective lung tissue recruitment than positive-pressure ventilation, which must overcome thoracic elastance. However, the higher incidence of hypercapnia in the NIVATS group likely reflects inadequate V/Q matching due to underlying pulmonary dysfunction (14) (urgent action is indicated when PaCO₂ >70 mmHg with pH <7.20).

Although the NIVATS group exhibited a higher incidence of arrhythmias and hemodynamic fluctuations—likely related to lighter anesthesia and increased sensitivity to surgical stimuli—these differences were not statistically significant. Notably, no life-threatening events occurred in either group. While previous studies have highlighted risks associated with high FiO₂ during OLV (18) and the benefits of permissive hypercapnia (19), our protocol prioritized physiological stability. Consistent with previous reports of conversion-to-intubation rates ranging from 2.8% to 11% (7,16,20,21), intraoperative hemorrhage was identified as the primary cause of conversion to thoracotomy in our study.

Intraoperative hemorrhage in tubeless surgery is primarily attributed to vascular injury secondary to cough reflexes or mediastinal oscillations during hilar dissection (8,9). The strategic administration of muscle relaxants before vascular ligation can suppress these physiological disturbances without compromising safety. Given that tubeless anesthesia carries increased risks for patients with prolonged procedures (>3 h), hypercapnia, excessive secretions, or obesity (BMI >30 kg/m²) (12), rigorous patient selection is essential. Accordingly, our institution applies a BMI threshold of ≤27 kg/m² for NIVATS. Advances in non-intubated techniques continue to mitigate these inherent risks (8,9,16).

Although cardiopulmonary complication rates favored NIVATS over intubated VATS, the difference was not statistically significant, likely due to sample size limitations. Nonetheless, the clinical benefits of NIVATS are evident. Vulnerable patients undergoing conventional VATS are susceptible to barotrauma, resulting in prolonged chest tube duration and increased drainage volume due to inflammatory responses (5,20). Conversely, NIVATS, by minimizing the use of opioid and muscle relaxant, accelerates postoperative rehabilitation—a benefit particularly relevant in elderly patients (2,3). Further, NIVATS significantly reduces the incidence of Postoperative Sore Throat (POST) [which has been reported in up to 57.5% of intubated cases (22,23)], thereby improving patient satisfaction. Importantly, our findings reinforce that conversion to intubation remains an essential safety measure for managing life-threatening hypoxemia, hemorrhage, or hemodynamic instability (8,9,16).

While NIVATS offers benefits in vacillating rapid recovery, concerns remain in relation to its effect on oncologic radicality. Some studies have reported no significant difference in lymph node dissection between intubated and non-intubated groups (5,7); however, other findings suggest that in elderly patients (>75 years), non-intubated techniques may result in fewer harvested lymph nodes (2). This is primarily attributed to a more restricted surgical field and the cough reflex induced by bilateral lung ventilation during mediastinal manipulation. Regarding long-term outcomes, conflicting data exist; one study reported improved 3-year survival with non-intubated anesthesia (24), while others found no significant difference in survival outcomes (2,25). Given that current survival data are largely derived from small retrospective studies, high-quality prospective trials are required to validate these findings.

Regarding tumor resection extent, this study strictly adhered to the principles of radical oncological resection based on lesion characteristics. Three surgical approaches—lobectomy, segmentectomy, and wedge resection—were employed. For subsolid nodules <2 cm, the risk of mediastinal lymph node metastasis is relatively low; thus, the effect of the number of dissected lymph nodes on long-term survival may be limited. Evidence also suggests that wedge resection can achieve long-term survival outcomes comparable to those of anatomical resection (4,12).

Contrary to previous concerns that spontaneous ventilation may compromise surgical visualization and lead to inadequate lymph node dissection (2), we found that the total number of dissected lymph nodes and the number of involved stations were comparable between the two groups. While short-term safety outcomes were favorable, the effect on long-term survival needs to be elucidated by ongoing follow-up.

Limitations

This study had a number of limitations. First, there is marked heterogeneity in the diagnostic criteria for impaired pulmonary function and inclusion thresholds, and a universally accepted standardized definition suitable for non-intubated surgery remains lacking, limiting the comparability of results across studies. The persistent imbalance in FEV₁ observed both pre- and post-PSM—stems from our clinical tendency to assign non-intubated anesthesia to patients with poorer pulmonary function. Second, as a single-center study with a limited sample size, the generalizability of our findings—particularly those regarding lymph node dissection—to institutions with different surgical volumes or levels of expertise requires caution. Third, although short-term outcomes (e.g., lymph node yield and the absence of severe adverse events) were favorable, the potential survival benefits of non-intubated anesthesia remain unproven. Further validation through systematic long-term follow-up and multicenter prospective studies is needed.

Conclusions

NIVATS for NSCLC patients with impaired pulmonary function is safe and feasible, and it facilitates rapid postoperative recovery while reducing complication rates. Successful implementation relies on close collaboration between experienced anesthesiologists and surgeons, strict adherence to surgical indications, and individualized anesthetic and surgical planning with established emergency protocols. Continuous perioperative cardiorespiratory monitoring is essential, and timely conversion to tracheal intubation should be performed when clinically indicated to ensure patient safety.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1637/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1637/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1637/prf

Funding: This work was supported by funding from the Joint Construction Program of Henan Province (No. LHGJ20240527).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2026-1637/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was approved by Institutional Ethics Board of Anyang Tumor Hospital (No. 2025KY05H01). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and applicable clinical practice guidelines. Informed consent was obtained from all patients enrolled in the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)