R01HL155760

The hemodynamic and metabolic effects of advanced circulatory support for resuscitation - There are over 350,000 victims of out-of-hospital cardiac arrest each year in the United States, and the success rates from cardiopulmonary resuscitation (CPR) average only about 10%.

In addition, organ shortage is the greatest challenge facing organ transplantation, with far fewer donors than needed, and many patients dying awaiting transplant. Approaches that could enhance survival from cardiac arrest, and also increase the number of organ donors, are, therefore, critically needed.

One approach is implementing systems to enhance blood flow during cardiac arrest, since enhanced flow increases survival. Even after 50 minutes of cardiac arrest, extracorporeal membrane oxygenation (ECMO) can double survival rates over those from conventional CPR.

More than half of cardiac arrest victims treated with ECMO do not, however, have return of spontaneous circulation (ROSC), and some patients with ROSC are brain dead. Patients with ongoing ECMO, but without ROSC, or with brain death, represent a large pool of viable donors.

Current ECMO systems, however, require substantial special training for vascular access, and a perfusionist, limiting their widespread use. Newer ECMO systems are being developed that allow more flow through shorter cannulas than with current systems.

It is not known, however, how much flow is needed for survival. If the critical amount of flow needed can be achieved with the shorter cannulas used with the newer systems, then shorter, easier to place, and less morbid cannulas can be used routinely, extending the use of ECMO to wider patient populations, including underserved areas.

We have developed an MRI compatible ECMO system and are using it while acquiring real-time magnetic resonance derived cerebral flow, oxygen metabolism, and metabolite levels. Study of these brain parameters is critical since brain function is the most important determinant of survival from cardiac arrest.

The hypotheses we are testing are that: 1) metabolic parameters and cerebral blood flow will be preserved by critical amounts of blood flow generated during resuscitation; 2) there are critical levels of blood flow that are needed during resuscitation for neurologically intact survival; 3) there are critical levels of metabolic parameters, brain injury biomarkers, inflammatory markers, and reactive oxygen species, measured during resuscitation, that predict neurologically intact survival; 4) adding CPR will reduce the amount of ECMO flow needed for survival; 5) intra-arrest hypothermia will reduce the amount of flow needed for survival; and 6) reactive oxygen species generated during resuscitation can be suppressed by critical levels of flow and hypothermia.

One goal of this program is to study the hemodynamic and metabolic effects of using an ECMO system that can be used without a perfusionist, and that uses cannulas that can be inserted percutaneously by a markedly increased pool of physicians.

Another goal is to understand the determinants of survival and the minimum amount of ECMO flow needed to improve survival. If successful, these systems should be able to deliver sufficient flow to increase neurologically intact survival from cardiac arrest and increase the number of organs available for transplant.

The Johns Hopkins University

NOT APPLICABLE

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Maryland United States

State-Wide

Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-19-056)

Amendment Since initial award the total obligations have increased 336% from $736,751 to $3,211,098.