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

our Patients

Terry Vanden Hoek, M.D. Associate Professor Medicine

Emergency Resuscitation CenterUniversity of Chicago and

Argonne National Laboratory

E R C

Conflict of interest disclosures:Conflict of interest disclosures:

Research funding from NIH, DODResearch funding from NIH, DOD

Preclinical hypothermia work includesPreclinical hypothermia work includes

patents for micropatents for micro--particulate ice slurryparticulate ice slurry

Other disclosures:Other disclosures:Mention of non-FDA approved devices for hypothermia

ObjectivesObjectivesHighlight new guidelines for cardiopulmonary Highlight new guidelines for cardiopulmonary resuscitation (CPR) and Emergency resuscitation (CPR) and Emergency Cardiovascular Care (ECC)Cardiovascular Care (ECC)

Discuss specific examples of translating new Discuss specific examples of translating new guidelines into the clinical settingguidelines into the clinical setting

Highlight need to develop physicianHighlight need to develop physician--scientists in scientists in Resuscitation MedicineResuscitation Medicine

Cardiac arrest survivalrates are not like those on TV—they have not changedsignificantly over 3 decades

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

Guidelines ProcessGuidelines ProcessInternational evidence evaluation process reviewed International evidence evaluation process reviewed topics in ECC and CPR.topics in ECC and CPR.

Review process extended over 36 months and Review process extended over 36 months and included 281 reviewers, completing 403 reviews on included 281 reviewers, completing 403 reviews on 276 topics. 276 topics.

Additional information: Additional information: www.C2005.orgwww.C2005.org

2005 Guidelines Changes2005 Guidelines Changes

AdvancedAdvancedCardiovascularCardiovascularLife Support Life Support

Science of ACLSScience of ACLS•• Recognize Recognize periperi--arrest conditionsarrest conditions•• Cardiopulmonary Resuscitation (CPR): Cardiopulmonary Resuscitation (CPR):

airway, ventilation, chest compressionsairway, ventilation, chest compressions•• Choreography of CPR with ACLS careChoreography of CPR with ACLS care•• DefibrillationDefibrillation•• Drug therapyDrug therapy•• PostPost--resuscitation careresuscitation care•• Emergency Cardiovascular Care:Emergency Cardiovascular Care:

ACS and StrokeACS and Stroke

Evidence Worksheets posted at: www.C2005.org

Science of ACLS: CPRScience of ACLS: CPR

Quality of CPR OutQuality of CPR Out--ofof--HospitalHospitalCase series n=176 (Stockholm, London, Case series n=176 (Stockholm, London, AkershusAkershus))

Outcome measure = G2000 standardsOutcome measure = G2000 standards

Chest compressions were not delivered 48% of Chest compressions were not delivered 48% of the timethe time

Most compressions were too shallowMost compressions were too shallow

ECG analysis and ECG analysis and defibdefib accounted for only a small accounted for only a small part of chest compression interruptionpart of chest compression interruption

Wik et al. JAMA 2005; 293:299Wik et al. JAMA 2005; 293:299--304304

Quality of CPR During InQuality of CPR During In--Hospital Cardiac ArrestHospital Cardiac Arrest

Case series n=67 (Chicago)Case series n=67 (Chicago)

Outcome measure = G2000 standardsOutcome measure = G2000 standards

Chest compressions were too slowChest compressions were too slow

Chest compressions not delivered almost 25% of Chest compressions not delivered almost 25% of the timethe time

38% of the compressions were too shallow38% of the compressions were too shallow

Ventilation rates were too highVentilation rates were too high

Abella B. Abella B. JAMAJAMA 2005; 293:3052005; 293:305--310310

Ventricular Fibrillation and CPRVentricular Fibrillation and CPR

Aortic pressure (purple)Aortic pressure (purple)

Right atrial pressure (yellow)Right atrial pressure (yellow)

Coronary Perfusion Pressure (Ao diastolic Coronary Perfusion Pressure (Ao diastolic -- RA diastolic)RA diastolic)

Swine myocardial blood flow and CPP after interrupted CPR (16 second pauses)

5050

6060

7070

8080

9090

100100

1010

1212

1414

1616

1818

2020

2222

YesYes

NoNo

YesYes

NoNo

MB

F, m

l/100

g/m

inM

BF,

ml/1

00g/

min

CPP

, mm

Hg

CPP

, mm

Hg

Berg RA et al: Circulation 2001;104:2465Berg RA et al: Circulation 2001;104:2465--7070

P<0.001P<0.001 P<0.001P<0.001

Neurologically normal 24Neurologically normal 24 --hour survival in swine with interrupted CPR (16 second pauses)

01020304050607080

YesYes

NoNo

Kern KB et al: Circulation 2002;105:645Kern KB et al: Circulation 2002;105:645 --99

P<0.0001P<0.0001

CPR and defibrillationCPR and defibrillation

Effects of interrupting chest compression on Effects of interrupting chest compression on calculated probability of successful defibrillation calculated probability of successful defibrillation

during outduring out--ofof--hospital cardiac arresthospital cardiac arrest

55101015152020252530303535404045455050

0 5 10 15 0 5 10 15 2020Duration of handsDuration of hands--off, seconds/minuteoff, seconds/minute

PP RO

SCR

OSC

, %, %

EftestolEftestol T et al: Circulation 2002;105:2270T et al: Circulation 2002;105:2270--33

n=156n=156

Healthcare Provider Healthcare Provider –– CPRCPRUniversal compression to ventilation ratioUniversal compression to ventilation ratio

All victims:All victims: 30:2 30:2 compressions to ventilationscompressions to ventilations ((single single rescuer).rescuer).Minimize interruptions. Allow for complete chest Minimize interruptions. Allow for complete chest recoil.recoil.Infant/child: Infant/child: 15:215:2 compression to ventilation ratio (2compression to ventilation ratio (2--rescuers).rescuers).

Healthcare Provider Healthcare Provider –– CPRCPRChange compressors (2Change compressors (2--rescuers) rescuers)

Change “compressor” role every 2 minutes or 5 cycles of Change “compressor” role every 2 minutes or 5 cycles of CPR.CPR.

Complete switch in 5 seconds or less.Complete switch in 5 seconds or less.

Translating New Guidelines into Clinical CPR Quality

Defibrillator customizedWith sensors to detect:

• Chest compression rate and depth• Ventilation rate and volume• Pulse presence or absence

Records entire arrest transcript for analysisAbella et al, 2005Edelson et al, 2006

ventilations

ECG

compressions

pulse check ECG: v fib

shock given

Arrest transcript

ECG: v tach

ECG

Even

tC

ompr

essi

on

Compression rate = 78 /min1:10 1:15 1:20

Examples of arrest data

Inappropriate shock for PEA

Vent

ilatio

nVentilation rate = 48 /min

3:35 3:40 3:45

<60 60-69 70-79 80-89 90-99 100-109 110-119 120-129 130-139

90

80

70

60

50

40

30

20

10

0

n = 401 segmentsmean rate 100.5 ± 21.5

chest compression rate (cpm)

num

ber o

f 30

sec

segm

ents

Chest compression rates

<10 10-19 20-29 30-39 40-49

200

180

160

140

120

100

80

60

40

20

0

n = 454 segmentsmean rate 22.9 ± 12.4

ventilation rate (vpm)

num

ber o

f 30

sec

segm

ents

Ventilation rates

Code Team Review

ACLS ACLS –– PostresuscitationPostresuscitationHypothermiaHypothermia

Unconscious adult patients with ROSC after outUnconscious adult patients with ROSC after out--ofof--hospital cardiac arrest (VF) should be cooled to 32hospital cardiac arrest (VF) should be cooled to 32ooC to C to 3434ooC for 12 hours. C for 12 hours.

Similar therapy may be beneficial for patients with nonSimilar therapy may be beneficial for patients with non--VF arrest outVF arrest out--of or inof or in--hospital arrest. hospital arrest.

Further research is needed.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 arrestComatose but hemodynamically stable In the Hypothermia after Cardiac Arrest (HACA)

study: 3,551 pts assessed, 275 enrolledOther 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 additionto cooling blanketrequired in about

70% of ptsto reach target temp

Cooling methods•Surface 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 oC

Cooling methods•Internal cooling

Cooling methods•Internal cooling

Cooling methods

•Internal cooling

Therapeutic hypothermia after cardiac arrest:

Practical considerations for protocol development and

implementation strategies

Therapeutic hypothermia after cardiac arrest:

Practical considerations for protocol development and

implementation strategies

http://www.therapeutichypothermia.com

Course FacultyCourse Faculty

Mary Ann Peberdy, MD, FACCAssociate Professor of Medicine and Emergency MedicineVirginia Commonwealth University

Terry L. Vanden Hoek, MDAssociate Professor of Emergency MedicineUniversity 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: 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

The FASEB Journal 14, 221-230 (2000)

•“As we enter the post-genomic era, physician-scientists will have the specialized perspectives required to lead evolving fields such as geneticmedicine, 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.”

Physician-Scientists are needed to close the gap between data/discovery and

new life-saving devices and treatments

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

Make path of research/discovery less difficult.So much informationSo little time & moneySo few mentorsSo little representation onNational funding committees

The FASEB Journal 14, 221-230 (2000)

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

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

University of Chicago and Argonne National Laboratory

“Health care providers, scientists and bioengineers working together to restore life after sudden death.”

Emergency Resuscitation Center

Clinical potential for new metabolicresuscitation strategies

0

25

50

75

100

Field ROSC Hosp Admit

HospD/C

# alive New treatments during CPR

Use new molecular vital signsto guide/optimizeCPR

1999, CPR; Weil and Tang ed.

VisionVisionSudden death patients who are currently

pronounced “dead” after sudden cardiovascular shock will routinely be resuscitated back to full

human function.

Mission Statement: Key GoalsMission 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 disciplinesDevelop world-class physician-scientists through formalized training programs--Laboratory and clinical rotation training

Provide hospital and community leadership in CPR/Resuscitation.

Translational ApproachTranslational Approach

Cellular basic science research

Translationalresearch Community

Bioengineering & Biotechnology

ERC CollaboratorsERC CollaboratorsAnesthesiology

Chun-Su YuanArgonne National Labs

Ken KaszaCarol Giometti

CardiologyBeth McNally

Emergency MedicineJames Rhee (Toxicology)Tom Fisher (Health Disparities)Linda Druelinger (Simulation)

Hospitalist MedicineDana Edelson

NeurologyJames Brorson

PediatricsGlyn DawsonJeremy Marks

Radiation/OncologyHoward Halpern

Pulmonary/Critical CareKimm HamannViswanathan NatarajanYimin Qin

Univ of MichiganSusan Stern

NorthwesternPaul Schumacker

Univ of WashingtonGraham Nichol

Virginia Commonwealth UniversityMimi Peberde

Medical College WisconsinTom Aufderheide

Univ of PennBen AbellaLance BeckerRaina MerchantRobert Neumar

Industry PartnersMedivanceGaymar IndustriesLaerdalPhilips

Ben AbellaJason AlvaradoTravis AndersonDavid BeiserWei-Tien ChangChang-Qing Li

ACKNOWLEDGEMENTS

Xinmin LiLance BeckerKimm HamannPaul SchumackerSue Stern

Juan LiYimin QinZuo-Hui ShaoHuashan WangKim WojcikDanhong Zhao