Saving Lives through Rapid Profound Hypothermia
EPR-Technologies, Inc., is a new biotechnology startup company that is a spinoff from the Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine.
EPR-Technologies is dedicated to the memory and vision of the founder of the Safar Center, Peter Safar, M.D. Our mission is to advance emergency medical resuscitation capabilities when cardiopulmonary resuscitation (CPR) fails by immediately inducing rapid profound hypothermia in the patient, in order "to save brains too good to die".
Dr. Safar was a pioneer in resuscitation research and is remembered as "the father of CPR”, as well as a world leader for public access to basic resuscitation procedures and a renowned international humanitarian.
The market for emergency medicine technology is quickly moving towards the portability of equipment and technology. This portability is essential to apply advanced capabilities by highly trained paramedics closer to the point of injury. EPR-Technologies is a key participant on the leading edge of these efforts to make rapid profound hypothermia following failed CPR a new standard of care.
The focus of the Company is to pursue commercial applications related to emergency profound hypothermia and resuscitation in cases of currently unresuscitable emergencies. The successful use of profound hypothermia will permit the stabilization of previously unrecoverable patients and allow time for transport of patients to medical centers and medical/surgical interventions and repairs under protected cardiac arrest. During this period, organ viability is preserved for up to 3 hours, followed by delayed resuscitation using cardiopulmonary bypass.
The Company’s initial products will be intended for use in (1) trauma centers, hospital emergency rooms, and in-hospital patient rooms, then (2) mobile ICU ambulances and helicopters, and eventually (3) other point-of-injury emergency/first-responder operations.
EPR-Technologies, Inc. plans to introduce novel emergency medical products that will support the rapid use of profound hypothermia in previously unrecoverable patients. These techniques will induce a three (3) hour state of tolerance to ischemia for any cause of cardiac arrest, thereby buying time for potential life-saving interventions. Our planned use of profound hypothermia in currently unresuscitable patients followed by delayed resuscitation is referred to as “Emergency Preservation and Resuscitation” (EPR).
The EPR products and services initially planned for development, marketing, and sale by the Company or through strategic alliances include the equipment, techniques, training, and decision support required to administer effectively each step of EPR in a hospital setting and eventually in an emergency/point-of-injury setting, together with the related, essential, disposable EPR medical products and cold perfusate solutions to save lives when CPR fails.
A Tribute to Peter Safar, M.D., "the Father of Cardiopulomary Resuscitation"
excerpts from: Therapeutic Hypothermia in Resuscitation: The Safar Vision
by Patrick M. Kochanek, M.D., Xianren Wu, M.D., Robert S.B. Clark, M.D., C. Edward Dixon, Ph.D., Larry Jenkins, Ph.D., Lyn Yaffe, M.D. and Samuel Tisherman, M.D., Safar Center for Resuscitation Research, Brain Trauma Research Center, Departments of Critical Care Medicine, Pediatrics, Anesthesiology, Neurological Surgery, and Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, and Alion Science and Technology, McLean VA, published 2003.
Much has been written about the incredible life of Peter Safar, inventor of modern day CPR, pioneer in anesthesiology, critical care medicine, emergency medicine and disaster reanimatology, and humanist and mentor to countless clinicians, scientists, and students. For any of you who are interested in learning more about this incredible man, a comprehensive review of Peter’s contributions to resuscitation can be found in a two-part series written by Peter Baskett and published in the journal Resuscitation (Baskett PJ: "Peter J. Safar, the early years 1924-1961, the birth of CPR", Resuscitation 2001;50:17–22; and Baskett PJ: "Peter J. Safar, Part 2, The University of Pittsburgh to the Safar Center for Resuscitation Research 1961-2002", Resuscitation 2002;55:3–7).
Peter Safar’s autobiography is also available through the Wood Memorial Library, and provides remarkable detail on both his academic and personal endeavors (Safar P: "From Vienna to Pittsburgh for Anesthesiology and Acute Medicine", Careers in Anesthesiology. Autobiographical Memoirs. Park Ridge, IL: American Society of Anesthesiologists, Wood Library-Museum, 2000, Wood Library Museum, 515 Busse Highway, Park Ridge, IL 60068). Finally, Drs. Patrick Kochanek, Ake Grenvik and John Schaefer, and Ms. Fran Mistrick assembled a Festschrift in honor of Dr. Safar, published in February 2004, as an entire freestanding supplement to the journal Critical Care Medicine (Kochanek PM, Grenvik A, Schaefer J, [Guest Eds], "A celebration of the life of Peter J. Safar, M.D., and Proceedings of the Second Annual Safar Symposium", Crit Care Med 2004; 32, Suppl: S1-S74). ...
Safar’s Definitions of Hypothermia and Its Use in Resuscitation
On the topic of therapeutic hypothermia in resuscitation, Peter Safar would always begin by pointing out two issues that he believed were critical about this area of study, namely, accurate and consistent terminology concerning the depth of hypothermia and the situation surrounding its use. He believed that hypothermia should be categorized into mild (34–36°C), moderate (27–33°C), deep (15–26°C), profound (10–14°C), and ultraprofound (<10°C), and that the consistent use of this terminology was important since different mechanisms are affected in each of these temperature ranges. ...
Peter Safar and Resuscitative Hypothermia in the 1960s to 1980s
Peter Safar was intimately involved in the use of therapeutic hypothermia in the 1960s in the treatment of patients across a broad spectrum of disorders during the birth of modern-day neurointensive care. He was heavily influenced by the work of Dr. Hugh Rosomoff in the Department of Neurological Surgery at the University of Pittsburgh, who was one of the pioneers in the investigation and application of therapeutic hypothermia in the 1950s and 1960s. ...
Safar also learned a great deal about therapeutic hypothermia in the early 1960s from the work of others outside Pittsburgh. For example, he was always intrigued by the work of Dr. Robert White in Cleveland, Ohio, who performed a number of pioneering studies of the use of hypothermia to preserve the isolated dog brain. Similarly, he also discussed the early use of hypothermia by Lundberg and co-workers in Lund, Sweden, and early use of spinal cord cooling by Albin. However, in retrospect, Peter Safar recognized that there was inadequate information available about how to optimize the application of hypothermia in that early era and that the side effects seen with the use of moderate hypothermia for prolonged periods (particularly pulmonary infection and sepsis) gradually led to its abandonment in clinical use.
In reviewing the collected works of Peter Safar, the earliest description of his thoughts on the use of therapeutic hypothermia are provided in an amazing article written by him and published in a 1964 issue of the Journal of the Iowa Medical Society. Peter Safar’s “ABCs” (and beyond) of resuscitation in the early 1960s are described in this article -- and of course Peter Safar was not satisfied with just ABC. He provided the resuscitator an entire alphabet of interventions for the victim in cardiac arrest. Prophetically, this describes the letter “H” in his resuscitation alphabet as the application of therapeutic hypothermia. This description is not all that far from what recently received a Level I endorsement from the International Liaison Committee on Resuscitation (ILCOR) and the American Heart Association (AHA). The figure outlining Peter’s ABCs from 1964 and the use of hypothermia is shown on the right below. ...
In the last 20 years, Peter Safar focused on the use of hypothermia since it was the only therapy that he found to consistently demonstrate a “breakthrough” effect in his experimental models. In 2002, two large clinical trials demonstrated the efficacy of mild hypothermia after ventricular fibrillation (VF) cardiopulmonary arrest in humans and, as previously described, this has now been recommended for clinical use by the key endorsing societies worldwide.
On the day that the ILCOR and AHA guidelines were published, endorsing mild hypothermia after VF cardiac arrest in adults, I (PK) went into Peter Safar’s office to share with him this exciting news. In typical Safar fashion he stated, “What took them so long?” When a therapy was shown to be effective -- based on sound experimental evidence in large-animal studies that included clinically relevant long-term outcome and intensive care unit (ICU) care, and that accurately modeled the clinical condition—Peter Safar believed that randomized clinical trials were needed only to show feasibility. Peter Safar was not convinced that randomized clinical trials (RCTs) were very helpful in the difficult setting of resuscitation medicine, where it is challenging to control any of the key physiological parameters or underlying disorders. He believed that if a therapy was shown to be feasible and safe in clinical trials, and effective in relevant laboratory models, we were depriving patients of a valuable therapy that may never be able to be proven effective in the morass of an RCT. Fortunately, mild hypothermia was powerful enough to demonstrate a beneficial effect in two RCTs. ...
Peter Safar and Resuscitative Hypothermia: Recent Investigation
Peter Safar also carried out a considerable body of work in the last 20 years to support the use of hypothermia on three additional fronts that are relevant to readership of TraumaCare. First, he worked closely with trauma surgeon and critical care physician Samuel Tisherman on the use of mild hypothermia to prolong the “golden hour” of shock. That work is in a highly controversial area because retrospective clinical studies associate exposure/secondary hypothermia with increased mortality rate. However, the studies of Safar and Tisherman in this area represent a substantial series of experiments in rodent and pig models of hemorrhagic shock, demonstrating that mild or moderate hypothermia can delay the time to exsanguination cardiopulmonary arrest in this condition. Second, he developed, after discussions with Colonel Ronald Bellamy of the United States Army, a novel approach to the resuscitation of victims of exsanguination cardiopulmonary arrest. He proposed inducing a brief (several-hour) state of suspended animation using an aortic flush of a cold preservative solution that could buy time for transport and surgical repair, which could be followed by delayed resuscitation using cardiopulmonary bypass. We at the Safar Center have been fortunate to participate in this landmark project, which, to date, has been able to successfully achieve good outcome in dogs after an exsanguination cardiopulmonary arrest of 2 hours’ duration using profound hypothermia (10°C). It will be interesting to see over the years that follow if clinical trials are carried out in either of these two extremely novel areas of research.
Finally, Peter Safar and co-workers also carried out some of the only contemporary work on the application of therapeutic hypothermia to the treatment of traumatic brain injury using large-animal models. Despite the considerable number of studies in contemporary models of experimental traumatic brain injury in rodents, few studies supported its use in large animal models, with clinically relevant long-term outcome, ICU care, and intracranial pressure (ICP) monitoring and control. ...
Peter Safar’s Overall Vision on the Potential of Therapeutic Hypothermia
Peter’s vision on hypothermia in resuscitation was that it was the most effective agent that was currently available in resuscitation medicine—and that it had important potential applications in at least 10 different disease processes, including 1) VF, asphyxial, and exsanguination cardiopulmonary arrest; 2) traumatic brain injury; 3) stroke; 4) acute myocardial infarction; 5) elective surgical procedures; 6) refractory status epilepticus; 7) septic shock; 8) spinal cord injury; 9) hemorrhagic shock; and 10) possibly even septic shock. He also believed that rigorous temperature control with prevention of fever in neurointensive care was logical and should be implemented. He believed that clinical feasibility and safety studies should be performed in each of these settings, followed by clinical application. ...
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