SPECIFIC AIMS The overall objective of this Program is to develop the TIVAPeds, an anesthesia ‘auto-pilot’ drug delivery platform designed to administer Total Intravenous Anesthesia (TIVA) in children 2-yrs and older. The proposed platform integrates a brain monitor whose output is used to automatically and continuously adjust the delivery of propofol based on the care provider’s targeted effect. We believe that this device will become an enabling technology facilitating the wider penetration of TIVA in pediatric anesthesia, both domestically and abroad, and will ultimately lead to a safer practice, and improved outcome. Rationale: TIVA has been shown to be a superior anesthesia regimen as compared to inhaled anesthesia with respect to intra-operative events and post-operative outcome [1]. In particular, the incidence of laryngospasms/bronchospasms, Post-Operative Nausea and Vomiting (PONV), and emergence agitation are significantly reduced [2]. For instance, TIVA with propofol and remifentanil was associated with a lower rate of emergence delirium (38.3% vs. 14.9%) and a lower postoperative pain score [3]. In addition, volatile anesthetics have been shown to be neurotoxic in the developing brain of all animal models tested to-date rats, mice, guinea pigs, piglets, and rhesus monkeys) [5, 25]. A recent study has shown a statistically significant association between cumulative exposure to inhaled anesthesia and worse full-scale/verbal/performance IQ and processing speed [27]. Other retrospective studies have reached similar conclusions with respect to learning disabilities [28, 29], development of attention-deficit/hyperactivity disorder [30], and deficits in language/abstract reasoning [32]. It is therefore not surprising that in some pediatric anesthesia departments, like the BC Children Hospital (Vancouver, BC, Canada), the use of TIVA has become the standard of care [4]. This comes in sharp contrast to the practice in the US, where inhaled anesthesia is still primarily used, mostly for reasons of convenience and training. Indeed, when using inhalation anesthetics, end-tidal volatile anesthetic concentration measures provide a real-time estimate of the volatile anesthetic concentration in the plasma blood. Complex pharmacokinetics effects are thus made transparent to the clinicians, who can adjust their titration accordingly. Similar methods are not available when using intravenous agents, which makes the practice of TIVA more difficult and error prone. Yet, in most countries, the use of TIVA has seen a steady increase over the last 15 years. This increase has been made possible by the availability of Target Controlled Infusion (TCI) pumps. These specialty pumps embed drug models that are used to calculate an infusion profile designed to quickly reach a steady-state drug blood plasma concentration, thereby accounting for the drug’s uptake, distribution, and elimination. However, the open loop nature of these pumps makes them prone to over/un...