New Life for the Treatment of Sudden Death: Translating New Guidelines to our Patients

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New Life for the Treatment of Sudden Death: Translating New Guidelines to our Patients Terry Vanden Hoek, M.D. Associate Professor Medicine Emergency Resuscitation Center University of Chicago and Argonne National Laboratory E R C

Conflict of interest disclosures: Research funding from NIH, DOD Preclinical hypothermia work includes patents for micro-particulate ice slurry Other disclosures: Mention of non-fda approved devices for hypothermia

Objectives Highlight new guidelines for cardiopulmonary resuscitation (CPR) and Emergency Cardiovascular Care (ECC) Discuss specific examples of translating new guidelines into the clinical setting Highlight need to develop physician-scientists scientists in Resuscitation Medicine

Cardiac arrest survival rates are not like those on TV they have not changed significantly over 3 decades

Guidelines for CPR and survival Guidelines for CPR and ECC are reviewed and updated every 5 years. Evidence evaluation process and consensus on science recommendations developed by International Liaison Committee on Resuscitation, of which AHA is a founding member. AHA Guidelines were developed by AHA ECC volunteer clinicians, scientists, and researchers.

Guidelines Process International evidence evaluation process reviewed topics in ECC and CPR. Review process extended over 36 months and included 281 reviewers, completing 403 reviews on 276 topics. Additional information: www.c2005.org

2005 Guidelines Changes Advanced Cardiovascular Life Support

Science of ACLS Recognize peri-arrest conditions Cardiopulmonary Resuscitation (CPR): airway, ventilation, chest compressions Choreography of CPR with ACLS care Defibrillation Drug therapy Post-resuscitation care Emergency Cardiovascular Care: ACS and Stroke Evidence Worksheets posted at: www.c2005.org

Science of ACLS: CPR

Quality of CPR Out-of of-hospital Case series n=176 (Stockholm, London, Akershus) Outcome measure = G2000 standards Chest compressions were not delivered 48% of the time Most compressions were too shallow ECG analysis and defib accounted for only a small part of chest compression interruption Wik et al. JAMA 2005; 293:299-304 304

Quality of CPR During In- Hospital Cardiac Arrest Case series n=67 (Chicago) Outcome measure = G2000 standards Chest compressions were too slow Chest compressions not delivered almost 25% of the time 38% of the compressions were too shallow Ventilation rates were too high Abella B. JAMA 2005; 293:305-310 310

Ventricular Fibrillation and CPR Aortic pressure (purple) Right atrial pressure (yellow) Coronary Perfusion Pressure (Ao diastolic - RA diastolic)

Swine myocardial blood flow and CPP after interrupted CPR (16 second pauses) MBF, ml/100g/min 100 90 80 70 60 P<0.001 Yes No CPP, mm Hg 22 20 18 16 14 12 P<0.001 Yes No 50 10 Berg RA et al: Circulation 2001;104:2465-70

Neurologically normal 24-hour survival in swine with interrupted CPR (16 second pauses) 80 70 60 50 40 30 20 10 0 P<0.0001 Yes No Kern KB et al: Circulation 2002;105:645-9

CPR and defibrillation

P ROSC, % Effects of interrupting chest compression on calculated probability of successful defibrillation during out-of of-hospital cardiac arrest 50 45 40 35 30 25 20 15 10 5 0 5 10 15 20 Duration of hands-off, seconds/minute Eftestol T et al: Circulation 2002;105:2270-3 n=156

Healthcare Provider CPR Universal compression to ventilation ratio All victims: 30:2 compressions to ventilations (single rescuer). Minimize interruptions. Allow for complete chest recoil. Infant/child: 15:2 compression to ventilation ratio (2- rescuers).

Healthcare Provider CPR Change compressors (2-rescuers) Change compressor role every 2 minutes or 5 cycles of CPR. Complete switch in 5 seconds or less.

Translating New Guidelines into Clinical CPR Quality Defibrillator customized With sensors to detect: Chest compression rate and depth Ventilation rate and volume Pulse presence or absence Records entire arrest transcript for analysis Abella et al, 2005 Edelson et al, 2006

Arrest transcript ventilations pulse check ECG ECG: v tach ECG: v fib shock given compressions

Examples of arrest data ECG Event Inappropriate shock for PEA Compression Compression rate = 78 /min 1:10 1:15 1:20 Ventilation Ventilation rate = 48 /min 3:35 3:40 3:45

Chest compression rates number of 30 sec segments 90 80 70 60 50 40 30 20 10 0 n = 401 segments mean rate 100.5 ± 21.5 <60 60-69 70-79 80-89 90-99 100-109 110-119 120-129 130-139 chest compression rate (cpm)

Ventilation rates number of 30 sec segments 200 180 160 140 120 100 80 60 40 20 0 n = 454 segments mean rate 22.9 ± 12.4 <10 10-19 20-29 30-39 40-49 ventilation rate (vpm)

Code Team Review

ACLS Postresuscitation Hypothermia Unconscious adult patients with ROSC after out-of of- hospital cardiac arrest (VF) should be cooled to 32 o C to 34 o C for 12 hours. Similar therapy may be beneficial for patients with non- VF arrest out-of of or in-hospital arrest. Further research is needed.

Thinking about the basics of therapeutic hypothermia Early patient identification: finding the group of cardiac arrest patients who will benefit most from cooling Cooling methods: external, internal, expensive and cheap Importance of a multidisciplinary approach

Patients who benefit from cooling therapy

Less than 10% of presenting cardiac arrest patients with return of spontaneous circulation (ROSC) were considered for cooling in clinical studies: Witnessed cardiac arrest Comatose but hemodynamically stable In the Hypothermia after Cardiac Arrest (HACA) study: 3,551 pts assessed, 275 enrolled Other selected inclusion/exclusion criteria: VF or pulseless Vtach as initial rhythmn Presumed cardiac origin No prolonged hypotension (MAP<60mmHg for >30min) or hypoxia ( O2 sat <85% for >15min)

Cooling methods Surface cooling Ice bags in addition to cooling blanket required in about 70% of pts to reach target temp

Cooling methods Surface cooling

Cooling methods Internal cooling --22 pts post ROSC who remained comatose --30ml/kg of ice-cold saline given via peripheral IV or femoral central line over 30 min after patient evaluated and paralyzed --Decreased core temp from 35.5 to 33.8 o C

Cooling methods Internal cooling

Cooling methods Internal cooling

Therapeutic hypothermia after cardiac arrest: Practical considerations for protocol development and implementation strategies http://www.therapeutichypothermia.com

Course Faculty Mary Ann Peberdy, MD, FACC Associate Professor of Medicine and Emergency Medicine Virginia Commonwealth University Terry L. Vanden Hoek, MD Associate Professor of Emergency Medicine University of Chicago http://www.therapeutichypothermia.com

From basic discovery to life-saving devices and treatments: How do we accelerate discovery? Critical Role of the Physician-Scientist

Physician-Scientists are needed to close the gap between data/discovery and new life-saving devices and treatments Physician-scientists: those individuals holding an M.D. or M.D./Ph.D. degree who perform biomedical research as their primary professional activity. The number of physician-scientists in U.S. has been declining for the last 2 decades, down 22% from 18,535 in 1983 to 14,479 in 1998. Ley TJ & Rosenberg LE. Removing career obstacles for young physician-scientists loan repayment programs. N Engl J Med 346, 368-372 (2002)

Physician-Scientists are needed to close the gap between data/discovery and new life-saving devices and treatments As we enter the post-genomic era, physicianscientists will have the specialized perspectives required to lead evolving fields such as genetic medicine, pharmacogenetics, and bioinformatics. As this research is translated into patient treatment protocols, it is physician-scientists who will have the necessary training and skills to ensure that these protocols are designed and evaluated in ethical and rigorous clinical trials. The FASEB Journal 14, 221-230 (2000)

Faxon D, Circulation 105, 1857-1860 (2002)

Make path of research/discovery less difficult. So much information So little time & money So few mentors So little representation on National funding committees The FASEB Journal 14, 221-230 (2000)

Nature Medicine 8 (5), 437-439 (2002)

Nature Medicine 8 (5), 437-439 (2002)

Emergency Resuscitation Center University of Chicago and Argonne National Laboratory Health care providers, scientists and bioengineers working together to restore life after sudden death.

Clinical potential for new metabolic resuscitation strategies # alive 100 75 50 25 0 New treatments during CPR Field ROSC Hosp Admit Hosp D/C Use new molecular vital signs to guide/ optimize CPR 1999, CPR; Weil and Tang ed.

Vision Sudden death patients who are currently pronounced dead after sudden cardiovascular shock will routinely be resuscitated back to full human function.

Mission Statement: Key Goals Restore life to victims of sudden death by developing innovative resuscitation strategies. Translate basic science discoveries into clinical diagnostic/therapeutic applications. Leverage multidisciplinary collaborations across relevant medical and scientific disciplines Develop world-class physician-scientists through formalized training programs --Laboratory and clinical rotation training Provide hospital and community leadership in CPR/Resuscitation.

Translational Approach Cellular basic science research Translational research Community Bioengineering & Biotechnology

ERC Collaborators Anesthesiology Chun-Su Yuan Argonne National Labs Ken Kasza Carol Giometti Cardiology Beth McNally Emergency Medicine James Rhee (Toxicology) Tom Fisher (Health Disparities) Linda Druelinger (Simulation) Hospitalist Medicine Dana Edelson Neurology James Brorson Pediatrics Glyn Dawson Jeremy Marks Radiation/Oncology Howard Halpern Pulmonary/Critical Care Kimm Hamann Viswanathan Natarajan Yimin Qin Univ of Michigan Susan Stern Northwestern Paul Schumacker Univ of Washington Graham Nichol Virginia Commonwealth University Mimi Peberde Medical College Wisconsin Tom Aufderheide Univ of Penn Ben Abella Lance Becker Raina Merchant Robert Neumar Industry Partners Medivance Gaymar Industries Laerdal Philips

ACKNOWLEDGEMENTS Ben Abella Jason Alvarado Travis Anderson David Beiser Wei-Tien Chang Chang-Qing Li Juan Li Yimin Qin Zuo-Hui Shao Huashan Wang Kim Wojcik Danhong Zhao Xinmin Li Lance Becker Kimm Hamann Paul Schumacker Sue Stern