Air insufflated in an uncontrolled manner through the endoscope results in wide fluctuations in intrathoracic and intraperitoneal pressures, overdistension of the gastrointestinal tract, and adverse hemodynamic effects. Von Delius et al. studied the potentional cardiopulmonary effects of transesophageal mediastinoscopy in a porcine model, using a conventional gastroscope [42]. Air insufflation Wortmannin solubility was manually performed and the pressure was monitored through the working port of the gastroscope. In 3 of the 8 pigs, there was pleural injury with tension pneumothorax, resulting in hemodynamic instability. In the remaining 5 pigs, median mediastinal pressure maintained was 4.5mmHg (mean 5.4 �� 2.2mmHg). In this uncomplicated mediastinoscopies, peak inspiratory pressures, pH, partial pressure of CO2, and partial pressure of O2 were not influenced.

Inadvertent high-pressure pneumomediastinum and pneumothorax have been major complications since the begining of thoracic NOTES [7, 12, 16]. Most authors use thoracic tube drainage for pressure relief. As CO2 pressure control is also a main concern in abdominal endoscopic surgery, new insufflators have been adapted to both deliver and monitor CO2 through the endoscope [43]. These may be of some use in transesophageal NOTES. Meanwhile, using a Veress needle or a transthoracic trocar may be a secure way to achieve good pneumothorax pressure control [18]. There is a great debate whether CO2 or room air should be used for transesophageal NOTES. CO2 is far more soluble in blood than air and fatal CO2 embolism is rare.

The effect of CO2 with respect to laparoscopy has suggested an overall attenuated inflammatory response Drug_discovery that may provide a further immunologic benefit. Conversely, room air laparoscopy has been shown to generate a greater inflammatory response, but a recent case-control study did not find a significant difference between the peritoneal inflammatory response of NOTES versus laparoscopy with CO2 and air pneumoperitoneum [44]. Even for intraesophageal endoscopic surgery, the question if either air or CO2-insufflation should be used is relevant. A study by Uemura et al. found a decreased need for midazolam in patients undergoing esophageal endoscopic submucosal dissection with CO2-insufflation when compared to air-insufflation. The authors attributed this decreased need for midazolam to decreased procedural pain [45]. In human POEM procedures, only CO2-insufflation has been used [26, 46]. Inoue et al. reported that none of the 17 patients in their series had postoperative subcutaneous emphysema, but CT scan just after procedure revealed a small amount of CO2 deposition in the paraesophageal mediastinum.