A fundamental question during assisted ventilation in the ICU is how to synchronize the ventilator rhythm with the patient's breathing effort smoothly and effectively. Dyssynchrony could lead to increased/wasted work of breathing, patient discomfort, increased need for sedation, higher rate of tracheostomy, longer durations of mechanical ventilation and reduced number of ventilator-free days, longer ICU and hospital stay, and lower probabilities of survival and home discharge. Current generation ventilators either dictate the breathing rhythm completely with the use of heavy sedation/muscle paralysis (ventilator-based ventilation) or let the patient trigger the ventilator breath by breath (patient-based ventilation). Neither extreme is optimal. We propose a next generation of ventilatory assist (entrainment-based mechanical ventilation, EMV) that is based on the classical physics theory of mutual entrainment between coupled oscillators, which may provide a cost-effective solution to this clinical problem. This innovative technique is motivated by our recent discovery that the brain circuits controlling breathing are capable of entraining to a ventilator and adaptin to it through learning and memory of the Hering-Breuer inflation reflex. In EMV, the patient's spontaneous respiratory rhythm and the ventilator rhythm are phase-locked to one another on the same tempo, just like two individuals dancing together. Under a previous NIH ARRA Challenge Grant (RC1) award we have implemented a prototype of EMV on a widely used mechanical ventilator (Puritan-Bennett Model 840) and demonstrated the feasibility of this novel technique on a computerized lung simulator. Based on these simulation results, a conditional approval for investigational device exemption has been recently granted by the FDA for initial clinical research of the EMV mode. To transition the base technology from the bench top to the bedside, a multidisciplinary research team comprised of a basic researcher/bioengineer (Dr. Poon, PI), a clinician (Dr. Harris, Co-I), a biostatistician (Dr. Schoenfeld, statistical consultan) and a technology developer (Covidien/Puritan-Bennett) has been formed to address the underlying scientific, engineering, statistical and clinical problems. The goal of this pilot projet is to first establish that the proposed EMV mode is both safe and effective in entraining the patient's breathing rhythm over a short (4-hour) period (Aim 1). This phase I clinical research wil allow us to fine-tune the parameters of the EMV mode in order to further minimize risks and maximize the effectiveness of the EMV mode in improving patient-ventilator synchrony over a long period. The second phase (Aim 2) is to establish that the EMV mode is safe and feasible in providing improved synchrony in ARDS patients when used over a patient's entire ventilation weaning period. The proposed phase I/phase II research are both necessary and sufficient for securing FDA approval of a full-scale phase III multicenter trial to be conducted in the future in order to test whether improved patient-ventilator synchrony with the EMV mode may lead to materially beneficial clinical outcomes during ventilator weaning.

Public Health Relevance

Mechanical ventilation is a basic life support procedure that is integral to any intensive care unit, emergency room, ambulatory unit or ventilator weaning facility, and is ubiquitous in many medical units and rehabilitation or long-term care facilities, including the patient's own home. However, for patients weaning from mechanical ventilation, dyssynchrony between the ventilator rhythm and the patient's spontaneous breathing rhythm could lead to increased/wasted work of breathing, patient discomfort, increased need for sedation, higher rate of tracheostomy, longer durations of mechanical ventilation and reduced number of ventilator-free days, longer ICU and hospital stay, and lower probabilities of survival and home discharge. This pilot clinical study will test a next-generation ventilatory assist mode called entrainment-based mechanical ventilation that is based on the classical physics theory of mutual entrainment between coupled oscillators, which may provide a cost-effective solution to this clinical problem.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Planning Grant (R34)
Project #
5R34HL125859-02
Application #
9144423
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Reineck, Lora A
Project Start
2015-09-15
Project End
2019-07-31
Budget Start
2017-06-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142