BME MS Thesis Defense - Jarred Mondonedo

Starts:
9:00 am on Friday, July 26, 2013
Location:
44 Cummington Mall, Room 203
COMMITTEE:
Bela Suki, PhD (Academic Advisor, BME)
David Kaczka, MD, PhD (Research Advisor, BIDMC)
Andrew Jackson, PhD (BME)
Brett Simon, MD, PhD (BIDMC)

TITLE: "Anesthetic Delivery System for Treatment of Status Asthmaticus"

ABSTRACT:
Status asthmaticus (SA) is a severe, acute exacerbation of asthma that is refractory to traditional therapies using standard bronchodilators and corticosteroids. Inhaled volatile anesthetics are currently used as a rescue therapy for SA due to their potent bronchodilator effects. However, it is unclear whether these agents act in vivo via 1) direct action on airway smooth muscle (ASM); 2) systemic re-circulation; or 3) autonomic reflexes from the central nervous system. Treatment with these agents can also lead to negative side effects, notably hypotension and arrhythmias, especially during prolonged pediatric use. The goals of this thesis were to compare direct versus systemic effects of these inhaled anesthetic agents, and to determine whether sufficient bronchodilation can be achieved via direct diffusion from the airway lumen to the ASM. We designed and developed a computer-actuated, ventilator-valve system to control the serial composition of the inspired gas. Using this system, we delivered inhaled anesthetic agents either a) to the anatomic dead-space selectively (direct), or b) continuously throughout inspiration (systemic) in three mongrel canines (20-25 kg) with methacholine-induced bronchoconstriction. Measurements of lung resistance (RL), elastance (EL), and anatomic dead space (VD) demonstrated that isoflurane and sevoflurane result in bronchodilation for both delivery regimes. This suggests that the mechanism of action for these agents is at least partly via direct effects. Fluctuations in were not directly coupled with those for or EL. Furthermore, there may exist a limit to maximal bronchodilation using inhaled anesthetics, with isoflurane being more potent. In summary, this study illustrates the feasibility of using a targeted anesthetic delivery to treat severe, acute bronchoconstriction. Such a delivery system has the potential to define a rapidly translatable treatment paradigm for SA while increasing patient safety.