NHLBI Workshop: Next Generation Resuscitation Research

Executive Summary

June 11, 2013

Purpose

On June 11, 2013, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in Bethesda, MD to discuss research topics and strategies to foster and facilitate the conduct of basic, translational, and clinical resuscitation science research.  The group was charged with developing a prioritized list of actionable recommendations to NHLBI for how to most effectively support research to improve resuscitation outcomes.  Workshop participants had expertise in cardiac electrophysiology, coagulation and hematology, emergency medicine, neurology, pediatrics, pulmonary critical care, and trauma research and practice. 

Emergency medical resuscitation represents an opportunity to forestall death following sudden cardiac arrest, respiratory failure, or massive blood loss after traumatic injury.  Despite improvement in resuscitation outcomes for these conditions, resuscitation is still all too often not effective.  For this reason, the present workshop was organized to provide NHLBI with recommendations about scientific opportunities and research priorities in this important area.  The workshop was organized as three consecutive roundtable discussions.  The first reviewed NHLBI support of resuscitation research following its June 2000 Post-Resuscitation and Initial Utility in Life Saving Efforts (PULSE) Workshop  and March 2001 PULSE Trauma Working Group.  The experiences and structures of the NHLBI-supported Resuscitation Outcomes Consortium (ROC) and the NINDS-supported Neurological Emergencies Treatment Trials (NETT) network, were presented, providing important lessons in the conduct of resuscitation research-oriented randomized clinical trials.  The NIH topic map system was used to describe the relationship of NHLBI-supported resuscitation science research to support provided across the entire NIH.  This encompassed 282 NHLBI grant awards, including those funded as a result of the following funding opportunity announcements:

Roundtable 2 focused on a description of scientific advances available for clinical testing and ways to build upon past research advances to fast-track promising ideas into clinical use as quickly as possible.  Through brief presentations by experts in cardiac electrophysiology, coagulation and hematology, emergency medicine, neurology, pediatrics, pulmonary critical care, and trauma research and practice, common needs and approaches were identified.  One interesting approach addressed was the possibility of using existing registries to address important clinical questions in a rapid and cost-effective manner.  In addition to the ROC Epistry—established to better define the incidence and outcome of out-of-hospital cardiac arrest and life-threatening traumatic injury; describe the relationships between resuscitation performance and the structure of various regional emergency medical services; and permit the evaluation the relationships between outcome and patient, EMS, regional, and periodic factors—the following other existing resources were identified: Nationwide Emergency Department Sample (NEDS), The State Emergency Department Databases (SEDD),  National Trauma Data Bank (NTDB), Get with the Guidelines-Resuscitation/ National Registry of Cardiopulmonary Resuscitation (NRCPR), and the Oregon Sudden Unexpected Death Study (SUDS).

Roundtable 3 focused on generating a set of prioritized and actionable recommendations to NHLBI for future opportunities to foster and support the next generation of resuscitation science research.  Discussion was enthusiastic as workshop participants strove to identify overarching, global themes and the most needed areas of future resuscitation science research emphasis.  Before reaching consensus of specific recommendations, participants spent time developing a short set of recommendations to address overarching research needs in resuscitation science research.  These global recommendations were that (1) all clinical studies should establish or contribute to an existing biorepository to aid in identification of biomarkers and possible genetic associations; (2) sources of “big data” should be identified and used to develop new resuscitation strategies to assist in clinical resuscitation decision-making; (3) different medical disciplines should be better integrated in emergency care to better provide rapid and organized responses to life-threatening medical emergencies; (4) alternative methods, like adaptive trial design, should be explored and used when developing future resuscitation trials; (5) trials initiated under an exception from informed consent should assure that patients are followed upon hospitalization and beyond discharge to capture quality of life outcomes; (6) the effect of age and its influence on resuscitation should be better assessed; and (7) pre-clinical models should be developed that more accurately reflect human emergency medical situations.  Upon completion of the discussions, three major areas of specific resuscitation research focus were identified:  (1) hemorrhage/hemostasis/coagulopathy, (2) primary and secondary neurologic injury, and (3) restoration of cardiac rhythm and improved cardiopulmonary resuscitation.  These are summarized below.

Recommendations

Hemorrhage/Hemostasis/Coagulopathy:

  • Develop new ways to quickly stop bleeding following traumatic injury associated with massive hemorrhage.  Well-designed mechanical devices and other non-surgical interventions are particularly needed for use in emergency care situations. 
  • Develop new, improved methods for earlier recognition and better treatment of internal bleeding.
  • Define optimal hemostatic resuscitation.  A better understanding is needed for the role of inflammation, coagulation therapies, reperfusion procedures, and biomarkers that provide an assessment of the extent of injury and effectiveness of therapy.  Development of better point-of-care testing procedures is needed.
  • Develop techniques to better assure neuroprotection before and while bleeding is stopped and blood flow is restored.

Primary and Secondary Neurologic Injury:

  • Develop better methods to prevent primary and secondary brain injury and predict which treatments can prevent patients from suffering irreversible neurological deficits following arrest and massive traumatic injury.
  • Better define the pathophysiologic characteristics of primary versus secondary brain injury, and identify biomarkers to better guide effective therapy and improve clinical outcomes.  Specific studies might be developed to optimize hypothermia protocols, or determine whether combination neuroprotective therapies plus hypothermia are effective in preserving and restoring neurologic function.
  • Define the role of neuroinflammatory mechanisms in contributing to brain injury as well as assuring brain repair.
  • Design studies to understand the biologic basis of pre-conditioning in the preservation of neural function after cardiac or respiratory arrest.  The mechanisms involved in these innate protective biologic processes may provide new therapeutic targets.

Restoration of Cardiac Rhythm and Improved Cardiopulmonary Resuscitation (CPR):

  • Design studies to define the genotype, phenotype, and underlying mechanisms of cardiac arrest due to pulseless electrical activity (PEA) and re-fibrillation.
  • Better define optimal cardiopulmonary resuscitation (CPR) methods and the physiologic and mechanical determinants of successful CPR.
  • Encourage the use of telemedicine to guide early resuscitation procedures.  Develop interrogative and therapeutic devices integrated with advanced communication systems to improve delivery of remote emergency medical care.
  • Design studies to determine if emergency extracorporeal membrane oxygenation (ECMO), or other methods to rapidly restore and maintain blood flow following cardiac arrest, may serve as an effective bridge to definitive therapy.

Workshop Chair

  • Gordon R. Bernard, MD – Vanderbilt University, School of Medicine

Workshop Roundtable Moderators

  • Jay W. Mason, MD – University of Utah, School of Medicine
  • Thomas M Scalea, MD – University of Maryland, School of Medicine
  • Walter J. Koroshetz, MD – National Institute of Neurological Disorders and Stroke, NIH

Workshop Participants

  • Neeraj Badjatia MD, MS – University of Maryland, School of Medicine
  • Bill G. Barsan, MD – University of Michigan Health System
  • Robert A. Berg, MD – The Children’s Hospital of Philadelphia
  • Peng-Sheng Chen, MD – Indiana University, School of Medicine
  • John B. Holcomb, MD – The University of Texas, Health Science Center at Houston
  • Kenneth Mann, PhD – The University of Vermont, College of Medicine
  • Raina Merchant, MD, MSHP – University of Pennsylvania, Perelman School of Medicine
  • Joseph Ornato, MD – Virginia Commonwealth University Medical Center
  • Polly Parsons MD – The University of Vermont, College of Medicine

NHLBI Staff

  • David A. Lathrop, PhD – Division of Cardiovascular Sciences
  • Debra Egan, MSc, MPH –Division of Cardiovascular Sciences
  • Andrei Kindzelski, MD, PhD – Division of Blood Diseases and Resources
  • Holly Krull, PhD – Division of Cardiovascular Sciences
  • Gail D. Pearson, MD, ScD – Division of Cardiovascular Sciences
  • George Sopko, MD, MPH – Division of Cardiovascular Sciences
  • Gail G. Weinmann, MD – Division of Lung Diseases

Last updated: July 18, 2013

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