Since the very beginning of the non-intubated thoracic surgery program, the feasibility of pulmonary resections of peripheral lung nodules has been one of the main objectives (1). The aim was to obtain histological characterization and extend a radical intended treatment to oncological patients unfit for general anesthesia or anatomic pulmonary resections. Growing pieces of evidence define the role of wedge resection in early-stage lung cancer treatment for nodules demonstrating a non-aggressive biological behavior, especially for frail patients unfit for anatomic resections (2). In particular, wedge resection demonstrated a higher overall 5-year survival and a lower recurrence rate compared to non-surgical strategies (3–5). General anesthesia with single lung ventilation has been associated with a higher risk of ventilatory-induced barotrauma and volotrauma as well as atelectasis in both the dependent and non-dependent lungs (6). Nonetheless, general anesthesia has been shown to impair the host immune system, eventually favoring both tumoral relapses and post-operative complications (7). Thus, non-intubated wedge resection seems to definitely balance tolerability with oncological radicality in highly selected patients. Main indications, surgical tips, and post-operative management strategies are, hereafter, presented.

First of all, general indications for wedge resection, as outlined in Table 1, should be verified. Nonetheless, frail patients unfit for an anatomic resection, presenting with more aggressive nodules, may be discussed in a multidisciplinary setting, including pulmonologists, oncologists, radiotherapists, radiologists, and thoracic surgeons in order to assess the functional reserve of the patients and to ensure the best clinical management. If the patient is fit for chemo or targeted therapies, surgical biopsy gives an adequate specimen for molecular characterization, allowing further medical-targeted therapies. Nonetheless, the non-intubated surgical biopsy, differently from computed tomography core needle biopsy, allows lymph node sampling, possibly affecting the treatment choice (8). In patients with low performance status, optimal surgical treatment is not allowed. In these patients, non-intubated wedge resection offers in the same minimally invasive procedure both a certain diagnosis as well as a definitive treatment.

Attention should be paid to general indications of video-assisted thoracic surgery (VATS). A clinical history at high risk of extensive pleural adhesions may hinder the thoracoscopic procedure. Successively, indications of non-intubated wedge resection should be verified (9). Particularly, a rapid resection with at least a 2-cm resection margin free of a tumor should be guaranteed. According to current guidelines, a parenchymal resection margin greater or equal to a nodule diameter is also considered adequate (2). Under this perspective, a nodule diameter and localization are crucial. As a general rule, the smaller the nodule, the easier the resection. In our experience, the cut-off may be set to 2 cm, but resection of larger nodules may be attempted. Localization of the nodule is the other key aspect. The nodule should be located peripherally, defined as the outer third of the lung, to allow quick nodule detection and resection, avoiding damages of main pulmonary vascular branches. Thus, the distance between the nodule and the visceral pleura may be shorter than the nodule diameter. In most of the cases, a length of 1 cm from the visceral pleura to the nodule is acceptable. Noticeably, an emphysematous pliable lung under spontaneous ventilation may help resect deeply located nodules—otherwise, unresectable. Nodules located deeper in the parenchyma may undergo resection if they are in proximity with the fissure but still far from the main vascular structures. Nodules located at the bases of the inferior lobe may be of concern due to the proximity with the inferior pulmonary vein. In these cases, as a first step, the pulmonary ligament should be sectioned in order to mobilize the inferior lobe and identify the inferior pulmonary vein. An accurate three-dimensional radiological planning should be made based on axial, sagittal, and coronal scans of a pre-operative computed tomography to localize the nodule. Finally, patient selection should also consider patient will and behavior. A very anxious patient may not tolerate the procedure. Defining contraindication to non-intubated wedge resection can be complex. The different components of the procedure should be carefully and singularly evaluated, and the best strategy should be tailored to patient characteristics. The main contraindications for the non-intubated wedge resection include both contraindications for non-intubated anesthesia and contraindications for thoracoscopic wedge resection as listed in Table 2 (10, 11).

The non-intubated program takes advances both from innovation in surgery and in anesthetic techniques. From triportalthoracoscopic access under thoracic epidural anesthesia (TEA) to uniportal thoracoscopic access under monitored-based anesthesia, surgical and anesthesiologic sciences have been integrated to reduce surgical invasiveness (1). In non-intubated surgery, spontaneous breathing and diaphragmatic contraction are preserved. As a consequence, the cough reflex is not inhibited and may hinder a surgical procedure. This physiologic side effect may be negligible in wedge resection because peripheral pulmonary manipulation only scarcely triggers the cough reflex. Whether a better control of cough reflex is mandatory for the surgical procedure, atropine (0.01 mg/kg) such as a vagal block (12), 5 ml of aerosolized 2% lidocaine or other techniques can be used (13, 14). Hereafter, the main characteristics of the different anesthesiologic techniques are presented.

The management of intraoperative complications may require orotracheal intubation and conversion to general anesthesia (29). In non-intubated wedge resection, anesthesiologic complications do not significantly differ from the ones characterizing other non-intubated procedures. These complications may require conversion to general anesthesia with or without conversion to thoracotomy. Hypercapnia leading to acidosis and hypoxemia is the most relevant (30). Hypercapnia is generally self-limiting. The so-called permissive hypercapnia follows the rebreathing phenomenon. Avoiding selective lung ventilation leads to air interexchange between lungs during surgical pneumothorax. However, this alteration is usually well-tolerated and goes to resolution at the end of surgery (22). Whether hypercapnia does not resolve or hypoxemia develops, high-flow oxygen masks or, if oxygen saturation is <90%, non-invasive Bilevel Positive Airway Pressure can be used, facilitating lung recruitment and adjusting a ventilation-to-perfusion mismatch. Difficulties in a nodule finding can follow insufficient deflation of the lung, unbearable cough, or extensive pleuro-parenchymal adherence. In the case of insufficient deflation of the parenchyma, additional small surgical access allows the introduction of a surgical instrument to retract the lung. If the patient is ventilated through a supra-glottic device, such as a laryngeal mask, ventilatory strategies to regularize breathing pulmonary movement may be applied, facilitating the resection. Strategies to control cough reflex have already been discussed. Energy devices can control pleuro-parenchymal adhesion as in conventional VATS. As afore-mentioned, it is pivotal to decide before the procedures a time cut-off before enlargement of the surgical access or conversion to general anesthesia.

Hemorrhages management depends mostly on the surgeon's thoracoscopic ability and can follow usual thoracoscopic guidance (31). It is remarkable that wedge resections rarely result in massive bleeding. If hemorrhages happen, a non-intubated thoracoscopic approach can be maintained if the surgeon can easily control the bleeding and the hemodynamic is deemed stable. Otherwise, urgent conversion in general anesthesia with or without thoracotomy is necessary.

Non-intubated thoracoscopic anatomic resections are technically demanding and require proficiency in thoracoscopic surgery, non-intubated surgery, and cardio-thoracic anesthesia. Nonetheless, in patients selected for non-intubated surgery, the pre-operative pulmonary function has to be carefully evaluated. Incautious anatomic resections in patients with marginal pulmonary function can be detrimental eventually leading to patient perioperative mortality. Therefore, at the beginning of the procedure, attention should be dedicated to assessing the resectability of the disease through a non-anatomic lung-sparing approach before any unreversible action.

As a general rule, conversion in general anesthesia with or without thoracotomy should never be considered as a failure but as a responsible decision for a patient's sake. Intubation and general anesthesia induction can be performed both in lateral decubitus or turning the patient in the supine position. In the latter option, a thoracic drainage device can be inserted in the chest cavity and one silk two stitch or surgical drapes can cover the surgical access to maintain sterility. During the change to supine position, the anesthesiologist becomes the team leader and controls head and neck (22).

Post-operative management of non-intubated wedge resection differs from the classical management of wedge resection performed under general anesthesia. In order to obtain the best results from the non-intubated technique, particular attention should be paid in strict adherent to enhanced recovery after surgery protocols (32). Patients can be early mobilized, and food and beverage oral intake can be restarted in the first hours from the procedure, thus avoiding intravenous fluids administration. Ambulation is strongly encouraged a few hours from the procedure. Pain control is achieved through oral analgesics and eventual intravenous moderate opioid-based analgesia (22, 33). A chest x-ray is performed between 2 and 8 h from the procedures, and chest drainage is removed as soon as no air leaks are detected and pleural collection is <200 ml in the day (24). Electronic drainage systems can be used. If air leaks persist longer than 6 days, dismission with a Heimlich valve can be considered. Comparing non-intubated VATS with VATS performed under general anesthesia, the former is associated with less post-operative complications and pain burden and a shorter hospital stay (34).

With the increase in life expectancy and the wide diffusion of high-resolution radiological imaging, pulmonary nodules are becoming a quite frequent occurrence. Growing pieces of evidence are supporting non-intubated thoracic surgery in different settings. In a recent randomized trial, non-intubated VATS demonstrated to be non-inferior in the treatment of spontaneous pneumothorax. Non-intubated approaches showed better results also in thymectomy, lung volume reduction surgery, interstitial lung disease, and several other procedures. Non-intubated wedge resection is one of the new frontiers in minimal invasive management of patients with lung cancer and may become a standard in the armamentarium of a thoracic surgeon. Appropriate patient selection and VATS expertise are crucial to obtaining good results.

VA: critical and scientific review of the manuscript. RT: writing the manuscript. AP: review of the literature. All authors contributed to the article and approved the submitted version.

This work was supported by post-graduate course funding.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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