TherApeutic hypothermia BY total liquid ventilation following cardiac arreSt and reSuscitation – ABYSS
“Sudden death” or out-of hospital cardiac arrest is a major public health issue. Only a few patients can be resuscitated and further survive, often with severe neurological sequels and a high socioeconomic cost. Implementation of a moderate therapeutic hypothermia (i.e., 32°C) is known to improve the survival and neurological recovery of those patients. However, this benefit primarily depends upon the rapidity to achieve the target temperature following cardiac arrest. Currently, most of the strategies used in critical care units provide a rather slow cooling rate (~-2°/h). Therefore, the need to dispose of specific devices inducing faster cooling rates is widely admitted.
In previous preclinical studies, INSERM U955-3 (partner of this project) investigated an original strategy to induce such an ultra-fast cooling through total liquid ventilation (TLV) with temperature-controlled perfluorocarbons (PFC) since these liquids can use the lungs as a heat exchanger while maintaining normal gas exchanges. Using experimental devices, this laboratory has established the solid proof of concept that hypothermic TLV can dramatically improves cardiac and neurological outcomes following focal myocardial ischemia and cardiac arrest in rabbits (pending US patent application). This demonstration also confirmed the innocuity of PFC.
The next mandatory step for a translation of hypothermic TLV in humans is to further investigate this approach in large animals. It accordingly requires a TLV device with two major features: (1) to be adapted for large animals (~80 kg) and (2) to accurately match both inspiratory and expiratory volumes to prevent volo/barotraumatism, while monitoring/controlling the corresponding pressure levels, flows and PFC temperature. Such a device does not exist on the market, and the experimental devices previously used cannot be modified to achieve the requested features.
Accordingly, the main goal of this project is to develop and validate such a TLV prototype in large animals. It will be designed to work with PFC already used in human therapeutic.
The development and validation of this TLV prototype will be permitted through a Consortium of four partners including an industrial company dedicated to technological innovations (BERTIN TECHNOLOGIES) and three academic laboratories specialized in the pre-clinical investigation of liquid ventilation (INSERM U955-3), in lung biomechanics (INSERM U955-13) and in lung imaging (CNRS UMR8081), respectively. The Consortium will be supervised by an Advisory Committee involving representatives from the medical community (expert clinicians), from “INSERM Transfert” and from the “ITMO Technologies pour la Santé” (AVIESAN). Depending upon the functional needs addressed by this Advisory Committee, the Consortium will produce a TLV prototype with a supervisor using an algorithm permitting to optimize lung filling/emptying as well as PFC-blood thermal exchanges. This algorithm will be constructed on the basis of a mathematical and physical modelization of PFC flows and thermal transfer thoroughly validated by fluorine imaging (MRI) of lungs filled with PFC. A first prototype will be adjusted to fit the size of small laboratory animals (3 kg), in order to validate the overall design, processes and safety/efficiency in rabbits. Then a second prototype will be dedicated and tested in a large animal model (pig) to further demonstrate its safety, efficiency and ability to induce faster cooling rates than other hypothermic strategies. This should provide the first proof of concept of the feasibility of hypothermic TLV in human-sized animals.
In the ultimate phase of the project, the Advisory Committee will allow to determine the expectations regarding a TLV device for pre-hospital ultra-fast cooling in human adults, and will make a synthesis step to determine the final inputs and regulatory experiments required to obtain a medical approval.
The total duration of the project is 36 months.
Monsieur Luc LOTTEAU (BERTIN TECHNOLOGIES SA) – email@example.com
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
BT BERTIN TECHNOLOGIES SA
IMRB U955 équipe 3 INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE - DELEGATION REGIONALEPARIS XII
U13 INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE - DELEGATION REGIONALEPARIS XII
UPS-IR4M UNIVERSITE DE PARIS XI [PARIS- SUD]
Help of the ANR 674,610 euros
Beginning and duration of the scientific project: December 2011 - 36 Months