Endoscopic insufflation, which was formerly conducted with air, is being substituted with carbon dioxide (CO2) in many pediatric clinics, despite the fact that there is little published evidence on its usage in children. We previously established that using CO2 during esophagogastroduodenoscopy (EGD) in non-intubated children causes temporary increases in end-tidal CO2 (EtCO2). This finding prompted worries regarding CO2 inhalation and systemic absorption. This problem is investigated here by monitoring both EtCO2 and transcutaneous CO2 (tCO2) during upper endoscopic operations in children. To evaluate if increased EtCO2 levels in non-intubated children experiencing CO2 insufflation during EGD are related to elevated systemic CO2 levels. A prospective, double-blind, randomized clinical experiment. For endoscopic insufflation, children were randomly assigned to either CO2 or air.