Background: In children, respiratory complications are the most frequent cause for harm when undergoing anesthesia. A large proportion of these complications arise from exaggerated laryngeal and respiratory reflex responses, particularly in children undergoing ENT surgery. Although the mortality of children undergoing adenotonsillectomies is low, these patients have a considerable risk of morbidity during the perioperative period. Apart from inadvertent laryngeal respiratory reflex responses (e.g., laryngospasm), postoperative emergence delirium and pain are frequent causes of discomfort in these patients. Because of the large number of children undergoing such interventions, an improvement in clinical outcome is of broad interest. Nonetheless, a comprehensive understanding of alleviating factors is largely lacking, because systematic trials remain sparse in the field of pediatric anesthesia. Previous work of our group, assessing laryngospasm prevention strategies, has revealed that intravenous (i.v.) administration of lidocaine was the most effective measure (relative risk reduction of 60%). However, laryngospasms could not be completely prevented, and the effect of a single bolus application appeared to be short-lived, making additional studies necessary to explore further improvements and to provide pharmacokinetic data for the safe and efficacious application of lidocaine. Furthermore, the differences in lidocaine metabolism, potentially based on pharmacogenetic properties, have not been examined in children. In addition, numerous experimental and clinical studies suggest that i.v. lidocaine may have additional beneficial effects: postoperative pain may be reduced (potentially anti-inflammatory effects) and emergency delirium may be prevented or attenuated. However, these effects have not been examined in a systematic manner in the clinical setting. On the other hand, lidocaine also has potential side effects, such as effects on pulmonary mechanics (increased airway resistance) and at the neuromuscular junction (impairment of neostigmine reversion) that are insufficiently examined, especially in the pediatric population considering their susceptible airways. Working hypothesis: The administration of systemic lidocaine tested in this project effectively reduces the incidence of laryngeal and respiratory reflex responses evoked by laryngeal stimulation (both in a clinical model using laryngeal stimulation and in a clinical study examining the effect caused by extubation). Furthermore, in children undergoing adenotonsillectomy the incidence of postoperative inadvertent airway reflexes, emergence delirium, and pain is reduced. Effects of lidocaine administration on airway mechanics and neuromuscular junction are expected to be of clinical relevance. Pharmacogenetic analyses will provide an explanation for part of the inter-individual pharmacokinetic variability observed in the metabolism of lidocaine. Specific aims: Studies addressing the abovementioned issues will permit a comprehensive understanding of the potential benefits and risks of systematic lidocaine application. Methods: We will use an array of established experimental and clinical techniques, such as a model of laryngeal stimulation, forced oscillation technique, accelerometry, and validated scales for the assessment of emergence delirium (PAED scale) and pain (age-adapted scales). Laboratory investigations will be performed in the collaboration with the Perioperative Safety Group (PD Dr. Th. Girard) of the Department Biomedicine, University Basel. Expected value of the proposed project: This project has implications for the clinical management of pediatric patients undergoing ENT surgery. It will provide a detailed assessment of pharmacokinetic/pharmacogenetic properties, clinical benefits and potential side effects of a systemic application of lidocaine in the context of contemporary anesthesia practice.