Non-Intubated Anesthesia Video-Assisted Thoracic Surgery for Subxiphoid Anterior Mediastinal Tumor Resection

Objective Subxiphoid approach for mediastinal tumor resection was reported to provide a better view and less postoperative pain. Non-intubated video-assisted thoracic surgery (NI-VATS) without muscle relaxant would decrease the possibility of postoperative airway collapse for anterior mediastinal mass operation. Herein, we sought to describe the use of NI-VATS through subxiphoid approach for anterior mediastinal tumor resection.


Introduction
Surgical resection is the main treatment for mediastinal neoplasms, both in malignant and benign tumors. Conventional median sternotomy is considered as the standard therapy, but video-assisted thoracic surgery (VATS) has gradually taken the place in decades. [1] The trans thoracic approach is the most common choice via VATS, however, the subxiphoid approach for anterior mediastinal tumor resection was reported to provide an excellent view of the bilateral pleural cavities and also be associated with reduction of the postoperative pain compared with trans thoracic approach. [2] General anesthesia might increase the postoperative risks for anterior mediastinal tumor resection. [3] The most feared complication is the airway collapse after intubation and muscle relaxation, which would potentially cause prolonged extubation after surgery. [4,5] Several studies have demonstrated that without using muscle relaxant and intubation, non-intubated VATS (NI-VATS) might solve this problem. [6] However, NI-VATS is rarely reported in subxiphoid approach for mediastinal tumor patients, which would limit the use of subxiphoid surgery when surgeon performing NI-VATS. In this study, we reported our initial experience and explored the feasibility and safety of NI-VATS management in anterior mediastinal tumor resection via subxiphoid approach.

Study design and patient inclusion
The data of all patients who underwent subxiphoid anterior mediastinal tumor resection at the rst a liated hospital of Guangzhou Medical University between December 2015 and September 2019 were identi ed and consecutively collected through electronic medical records. The study protocol and methods were reviewed by the institutional ethics committee of hospital. Informed consents were obtained from every patient. Exclusion criteria: cases that underwent median sternotomy, cases that underwent trans thoracic approach surgery, malignant cases with obvious invasion to the surrounding organs. All patients were evaluated by thoracic surgeons before operation. Computed tomography (CT) scans of all patients were performed to con rm the size and position of lesions by two independent radiologists. Prior to the surgery, anesthetists visited each patient to judge who could be potentially received non-intubated surgery. Patients who underwent NI-VATS comprised the experimental group, and patients who received intubated VATS (I-VATS) comprised the control group.
Contraindications to NI-VATS: American Society of Anesthesiologists (ASA) class 4 or greater, body mass index (BMI) 30 or greater, severe heart disease (e.g., ischemia, arrhythmia, etc.), hemodynamic instability, coagulopathy, asthma and sleep apnea syndrome. [7] All patients met the criteria were asked whether they would like to receive new technique of NI-VATS, patients who refused would get the conventional intubated surgery.

Surgical procedures
The surgical process is the same between NI-VATS and I-VATS groups via mediastinal approach (Fig. 1). Details of the surgical procedure have been already reported elsewhere. [8] A 3-cm incision was made 2 cm below the lower edge of the xiphoid for setting the thoracoscope. Two 5 mm extra pleural thoracic ports were created at the midclavicular line intersecting with the bilateral costal arch to introduce a thoracoscopic grasping forceps and a harmonic scalpel. A pneumomediastinum was created by an 8 cm H 2 O positive pressure carbon dioxide (CO 2 ) insu ation to enlarge the retrosternal space and facilitate dissection of the tumor. Both the right-sided and left-sided mediastinal pleura were opened. The incision in the chest wall could cause collapse of the lungs. The tumor and surrounding tissue were resected and removed through the subxiphoid port. Finally, the air in the chest cavities was evacuated by in ating the lungs. A drainage tube was inserted into the mediastinum through the subxiphoid incision. If necessary, the process was changed from the subxiphoid approach to the trans thoracic approach or open thoracotomy.

Data collection and Statistical analyses
Baseline characteristics including age, BMI, gender, tumor size, histology and myasthenia gravis status were extracted to observe the balance between two groups. The clinical data included intraoperative blood loss, anesthesia time, operation time, hospital duration after surgery, postoperative chest tube duration, postoperative drainage volume and pain evaluation. Continuous data are presented as mean and standard deviation and were analyzed with 2-sample Student t tests for independent data.
Categorical variables are given as a count and percentage of patients and compared with the X 2 or Fisher exact test. All statistical tests were 2-sided. P values of less than 0.05 were considered signi cant. SPSS software (SPSS version 25.0; IBM Corp, Armonk, NY) was used for all data analysis. [9] Results Patients characteristics A total of 40 patients between December 2015 and September 2019 underwent subxiphoid VATS anterior mediastinal tumor resection were consecutively included in this analysis. (Fig. 2) Among them, 21 patients received NI-VATS (52.5%) and 19 patients were treated under I-VATS (47.5%). The baseline characteristics were summarized in Table 1. Baseline demographic and clinical variables were well balanced between the two groups. Operative results and postoperative recovery No surgery-related deaths occurred. In total, operative/anesthesia related intraoperative complications were similar in NI-VATS groups and I-VATS (2/21 vs. 4/19; p = 0.446). Speci cally, two patients in the I-VATS group and one patient in NI-VATS group were converted to the trans thoracic approach due to an excess of fat tissues. Two patients in the I-VATS group and one patient in NI-VATS group were switched to median sternotomy due to the pleural adhesions.
The incidence of post-operative complication was less in the NI-VATS and NI-VATS group, although without signi cant statistical (5/21 vs 7/19; p = 0.369). No nerve damage or prolonged extubation owing to airway collapse occurred in both groups. All perioperative complications were summarized in Table 2.

Discussion
This is the rst cohort study on subxiphoid NI-VATS mediastinal tumor resection, which indicated that NI-VATS was a safe and feasible procedure via subxiphoid approach. Although statistically signi cant was not observed because of small sample size, NI-VATS might potentially decease perioperative complication compared with I-VATS (7/21 vs 11/19). It can be considered as an alternative to I-VATS when lateral approach is not available or when surgeons preferred subxiphoid surgery.
Compared with the trans thoracic approach, the most prominent advantages of subxiphoid approach for mediastinal tumor are more visual and less postoperative pain. [10] A complete resection of tumor is the primary aim. With the help of a camera scope inserted from the midline of the body, it would be convenient to look over the bilateral mediastinum clearly and con rm the location of important blood vessels and nerves nearby. [11] However, there are still some shortcomings of subxiphoid approach. First, a surgical team familiar with the subxiphoid approach procedure is needed. Second, it's hard to play when severe adhesions are existing. Third, the tumor size also need to be limited because of the narrow space. [8] Therefore, the application of the subxiphoid approach may be restricted in some conditions.
The anesthesia process of the I-VATS group in subxiphoid approach is almost the same as it in other thoracic surgeries. [12] When using a double-lumen tube for one-lung ventilation, contralateral lung collapse is easy to achieve via gentle press by a surgeon and air suction by an anesthesiologist.
Nonetheless, the anesthesia process of the NI-VATS group under subxiphoid approach is a novel attempt. There was only one case report about subxiphoid NI-VATS for thymectomy in 2017; the patient was selected carefully, which indicating that NI-VATS in subxiphoid approach was still under exploring. [13] The present study indicated that NI-VATS under subxiphoid approach was a feasible procedure with similar intraoperative and postoperative outcomes with conventional I-VATS group, which Spontaneous ventilation during surgery relies on the integrality of at least one side of pleura. The way of three-port subxiphoid approach in our study cuts bilateral mediastinal pleuras, causing collapse of both sides of lungs, which made complete spontaneous ventilation impossible. When there is bilateral pneumothorax at the same time, mediastinal swing would stop, followed by a continuous de ation and in ation of bilateral lungs, which would bring great challenge to the surgeon. To alleviate this problem, we adopted a small tide volume (3-4L/min) ventilation through SIMV mode, which would not only maintain the oxygen supply but also minimize the impact on the operation.
Non-intubated anesthesia management for subxiphoid approach actually includes laryngeal mask airway general anesthesia (without muscle relaxant) in SIMV mode, combined with vagus and intercostal nerve blocking. The laryngeal mask could potentially avoid intubation-associated complications, including postoperative sore throat, hoarseness and irritating cough. Besides, the di cult intubation is not uncommon in thymoma patients, rendering a laryngeal mask the preferred option. [6,7] Not using muscle relaxants is bene t for myasthenia gravis patients, which can avoid the residual effects of muscle relaxants, achieve faster recovery of respiratory muscle function and lower the incidence of di cult postoperative extubation. [14] The bene ts of omitting muscle relaxants are not limited in myasthenia gravis patients, it was reported that the use of muscle relaxants was associated with an increased risk of postoperative pulmonary complications, which cannot be reduced by the administration of reversal agents like sugammadex. [15] In addition, muscle relaxants during large anterior mediastinal tumor resection would cause airway collapse, NI-VATS would potentially avoid this situation. [6] Although no airway collapse or prolonged extubation case occurred in our study, it could happen when the mediastinal mass is big. One of the important meanings of this study is to prove the feasible and safety of NI-VATS under subxiphoid approach. When surgeons confront a situation when convention I-VATS may have the high risk of causing airway collapse, he/she could also use NI-VATS via subxiphoid approach.
There are several limitations in our study, including small sample size, short follow-up and retrospective nature. Because the process is relatively novel, the steps are unfamiliar, and good cooperation is needed between the surgeons and the anesthesiologists, this new approach was not commonly performed.

Conclusion
In summary, this study reveals that NI-VATS mediastinal tumor resection is a safe and technically feasible option. This technique leads to comparable postoperative outcomes when compared with I-VATS.