Device for Multi-Frequency Oscillatory Ventilation in Adult Patients with the Acute Respiratory Distress Syndrome

Project SummaryAbstractRespiratory failure from the acute respiratory distress syndromeARDSaccounts formillion ICU days annually in the U Splacing a significant burden on public health resourcesLung protective ventilation relies on positive end expiratory pressurePEEPto limit end expiratory derecruitmentand low tidal volumes to reduce inspiratory overdistentionWhile such ventilatory strategies have significantly improved outcomes in ARDSmortality nonetheless remains highSince ventilation distribution in ARDS is governed by a heterogeneous distribution of regional mechanicsthe most appropriate distending pressureventilation frequencyor tidal volume for one lung region may not necessarily be the same for anothereven in the same patientThis may result in substantial regions of the lung being underor over ventilatedwith poor ventilation to perfusion matching and increased dead spaceRecentlywe demonstrated that lung function and gas exchange can be significantly improved in heterogeneous preterm lungs if volume oscillations are applied at multiple simultaneous frequenciesrather than at a single discrete frequencyKaczka et alAnesthesiologyWe termed this unique modality of mechanical ventilation asMultiFrequency Oscillatory VentilationMFOVand proposed that such improved physiologic outcomes arose from the more even distribution of ventilation to different lung regionsin accordance with local mechanical propertiesHoweverthe ability to generate high fidelity MFOV waveforms in large animal test subjects or adult human patients is severely limited by existing ventilator technologyExperimental systems currently used for generating oscillations are not capable of providing high amplitude flows or maintaining the respiratory system at a constant mean pressure during excitationThusthe OscillaVent Randamp D teamandapos s overall goal for this Phase I STTR application is to establish the feasibility of developing a commercially viable hybrid ventilator oscillator capable of generating MFOV waveforms for use in adult human ARDS patientsas well as in large animalsas research subjectsThe envisioned device will also be capable of generating conventional ventilator waveformsIn Aimwe propose to develop a prototype ventilator oscillator capable of generating flowstidal volumesand airway pressures at frequencies over ranges typically used for adult human conventional ventilation and oscillationas well as MFOVIn Aimwe will demonstrate that our prototype ventilator oscillatorand MFOV in particularis capable of maintaining gas exchange in a large animal under baseline conditions and during heterogeneous lung injuryBased on our teamandapos s decades of expertise and strong preliminary datathe results obtained from this Phase I STTR project will have a high likelihood of establishing the foundation for a device capable of a newviable mode of oscillatory ventilation in a broad range of respiratory failure patientsPhase I success will set the stage for the larger Phase II demonstration project that will provide the validation data needed to engage investors and or licensing partners for STTR Phase IIB Phase III commercialization Project Narrative Acute respiratory distress syndromeARDSis a devastating lung condition that affects almostAmericans yearlyThe mainstay of treatment for ARDS is conventional mechanical ventilationwhich can inadvertently worsen existing lung injury via overdistension and cyclic recruitmentderecruitmentThe goal of this project is to develop a novel device capable of providing an alternative ventilation strategytermedMulti Frequency Oscillatory VentilationMFOVfor better treatment in these difficult to manage patientsand to attain much better health outcomes for those with ARDS