Page 1

Joseph P. Ornato, MD, FACP, FACC, FACEP

Professor & Chairman, Dept. of Emergency Medicine
Professor, Internal Medicine (Cardiology)
Virginia Commonwealth University Health System
Operational Medical Director
Richmond Ambulance Authority
Richmond Fire & EMS
Henrico County Division of Fire
Richmond, VA
Cutting Edge Advances & Controversies
in Cardiopulmonary Resuscitation
Objectives
Discuss controversial issues & latest advances in
CPR technique and sequencing
Review the evidence & ongoing studies on whether
ACLS drugs are of value during resuscitation
Should we avoid hyperoxygenating patients?
Discuss the evolving science regarding the
prehospital use, optimal duration, depth, and target
for cooling in therapeutic hypothermia
Review next generation technology for protecting the
brain during and after resuscitation
Public Health Burden of Cardiac Arrest
Heart Disease and Stroke Statistics 2012 Update
A Report from the American Heart Association
Go et al. Circulation. 2013;127:e6-e245
# Cardiac
Arrests/yr
Survival
rate
Mortality
rate
# deaths/yr
in USA
Out-of-hospital 359,400 9.5% 90.5% 325,257
In-hospital 209,000 24.2% 75.8% 158,422
Total 483,679
Equivalent loss of life
4 Boeing 747 aircraft crashing
& killing everyone on board
each day of the year!
Regional variation in OOH-CA survival
Nichol et al. JAMA 2008; 300:1423-31
Overall survival to discharge (n= 19,584) = 4.4%
Resuscitation Outcomes Consortium (ROC)
268 EMS and fire agencies
35,000 square miles
24 million people
3,500 EMS vehicles
30,000 EMS personnel
100 IRBs
289 hospitals
Dallas
Portland
Alabama
Seattle-King
County
San Diego
Toronto
Pittsburgh
Vancouv er
Milwau
kee
Data Coordinating
Center, Seattle
Ottawa
CPR Technique
CPR technique
Rate
Downstroke force & depth
Upstroke relaxation
Chest compression fraction
(CCF)
Pauses
Compression:ventilation
sequence
CPR chest compression rate
Abella B S et al. Circulation 2005;111:428-34
97 in-hospital arrests
3 hospitals
Chest compression force & depth
Stiell I et al. Crit Care Med 2012; 40:1192-8
1,029 adult patients from 7
US/Canadian EMS systems in
ROC Epistry
Quality CPR data from 2006-9
Found inadequate compression
depth in 50% of patients by
2005 GLs (1.5-2), nearly 100%
by 2010 GLs (at least 2)
2 1.5 1.0
2 1.5 1.0
Incomplete chest wall decompression during CPR by EMS
personnel
Aufderheide et al. Resuscitation 64 (2005) 353362
Page 2
Effect of incomplete chest wall decompression on coronary and
cerebral perfusion pressures during CPR in swine
Yannopoulos D et al. Resuscitation 2005;64:363-72
n=9 instrumented swine
6 minutes untreated VF standard CPR* x 3 min CPR with 75% recoil (residual 1.2
cm sternal compression @ end decompression) x 1 min standard CPR* x 1 min
defib x 3 ACLS
0
5
10
15
20
25
100% 75%
Coronary
PP
[mm Hg]
p< .05 Critical
pressure for
ROSC
(Paradis,
JAMA
1990;263:32
57-8)
0
2
4
6
8
10
12
14
16
100% 75%
Cerebral
PP
[mm Hg]
p< .05
% Chest Wall Decompression % Chest Wall Decompression
Chest compression fraction vs. ROSC
Vaillancourt et al. Resuscitation 2011; 82:1501-7
Effect of chest compression pauses
on coronary perfusion pressure
Pauses in CC during CPR in humans
Porter TR, Ornato JP, et al. Am J Cardiol 1992; 70:1056-60
Preshock, postshock, and perishock pauses
Cheskes S et al. Circulation 2011;124:58-66
10
sec
10-20
sec
>20
sec
10
sec
10-20
sec
>20
sec
10
sec
10-20
sec
>20
sec
How long should you
Prime the Pump before shocking VF?
Theoretical importance of myocardial ATP
Myocardial Cell
100%ATP
Myocardial Cell
<10%ATP
Myocardial Cell
30-40%ATP
RV dilation during pauses in chest compression
Courtesy of Dr. Stig Steen
University Hospital, Lund, Sweden
Early versus later rhythm analysis in patients with out-of-
hospital cardiac arrest
Stiell IG, et al. N Engl J Med. 2011;365(9):787-97
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Do ACLS drugs
improve outcome?
Benefit of each link in the chain of survival
Stiell I et al. N Engl J Med 2004;351:647-56
1.6 [1.2, 2.3]
4.4 [3.1, 6.4]
3.7 [2.5, 5.4]
3.4 [1.4, 8.4]
1.1 [0.8, 1.5]
ccv
Variable
Age <75 yr
Early Access
Early CPR
Early DF
Early ACLS
Adjusted Odds Ratio [95%CI]
ccv 0.1 1.0 10.0
Adjusted Odds Ratio [95% CI]
Survival worse Survival better
5,638 OOH-CA patients
17 cities in Ontario, CA
Sequential addition of each link in
the chain of survival
Outcome= survival to hospital
discharge
ACLS meds vs. no ACLS drugs in Oslo
Olasveengen TM et al. JAMA 2009; 301:2222-9
851 OOH-CA
cases
Randomized to
ACLS with vs.
without drugs
EMS response time
interval= 10 min
Initial VF= 33%
Byst witn= 65%
Byst CPR= 63%
MD on unit= 37%
Prehospital randomized trial of no epi vs. epi
Jacobs I et al. Resuscitation 2011;82(9):1138-43
8%
13%
2%
24%
25%
4%
0%
5%
10%
15%
20%
25%
30%
ROSC Admitted Discharged
No epinephrine Epinephrine
p <0.001
p <0.001
p =.15
534 prehospital cardiac arrest pts
Randomized to no epi vs. epi
Perth, Australia
Prehospital epinephrine use & survival in Japan
Hagihara A et al. JAMA 2012; 307:1161-8
Model
ROSC
Unadjusted
Adjusted for propensity
Adjusted for propensity and selected variables
Adjusted for all covariates
1 month survival
Unadjusted
Adjusted for propensity
Adjusted for propensity and selected variables
Adjusted for all covariates
CPC 1 or 2
Unadjusted
Adjusted for propensity
Adjusted for propensity and selected variables
Adjusted for all covariates
OPC 1 or 2
Unadjusted
Adjusted for propensity
Adjusted for propensity and selected variables
Adjusted for all covariates
Odds Ratio [95% CI]
Favors No
Prehospital Epinephrine
Favors
Prehospital Epinephrine 417,188 OOH-CA
cases
EMS skills:
CPR
AED
IV
Give epi 1 mg
q4min x 3
Epinephrine vs. no
epinephrine by EMS
3.7% of patients
received epinephrine
Antiarrhythmic drugs for VF/pVT
American Heart Association 2010 ACLS Guidelines
Amiodarone or lidocaine (each is a class Iib may be considered
recommendation for shock-refractory VF/VT)
Amiodarone and lidocaine may have other adverse effects
Neither drug has been proven (or tested adequately) to improve
survival to discharge
Unproven therapies may be . . .
Beneficial
Inconsequential (make no difference)
Harmful
The only way to know if lidocaine or amiodarone work is to
compare either against placebo
Persistent or
recurrent VF/VT
IIb medications
Lidocaine
Bretylium
Mg sulfate
Procainamide
(Na bicarb)
Continue CPR
Intubate at once
Obtain IV access
Epi 1 mg IV q 3-5 min
DF 360 J within 30-60 sec
DF 360 J 30-60 sec after med dose
Pattern drug-shock , drug-shock
Placebo Amio 300 mg
Amiodarone vs. lidocaine OOH-CA
N= 504
Kudenchuk P et al. N Engl J Med 1999; 341:871-8
N= 348
Amio vs. Lido
Toronto EMS
911-1
st
DF = 127 min
911-drug = 258 min
Dorian P et al. N Engl J Med. 2002
Mar 21;346(12):884-90
ROC Amiodarone vs. Lidocaine vs. Placebo Study
(ALPS)
N=
SYRINGE #
AMIODARONE
KIT
LIDOCAINEKIT PLACEBO KIT
1
Amiodarone
150 mg (3
cc)
Lidocaine60
mg (3 cc)
Placebo (3
cc)
2
Amiodarone
150 mg (3
cc)
Lidocaine60
mg (3 cc)
Placebo (3
cc)
3
Amiodarone
150 mg (3
cc)
Lidocaine60
mg (3 cc)
Placebo (3
cc)
Should we avoid hyperoxygenating
patients post-ROSC?
Page 4
Metabolic Chain of Events in Cardiac Arrest
Cardiac
Arrest
No Blood Flow Cerebral Ischemia
O
2
Reperfusion Free Radicals
Cell Death and Cerebral injury
CPR /
Pulse
Cell Damage
Post Cardiac Arrest Syndrome
Unique pathophysiologic process involving multiple
organs
Whole body ischemia
Global tissue and organ injury
Reperfusion injury
On-going inflammation and injury
Key components
Post arrest brain injury
Post arrest myocardial dysfunction
Systemic ischemia / reperfusion response
Reperfusion Injury After CA
Brain and heart more vulnerable to ischemic injury
Intrinsic high oxygen consumption and low tissue
oxygen storage capacity
Increase in Hgb saturation in brain and myocardial
vasculature to above baseline levels reperfusion
hyperoxia
Oxygen paradox
Oxygenation Post ROSC
Ventilation with 100% oxygen in the first
hour after experimental CA results in
worse neurologic outcomes
Multiple species
Cells in a high O2 environment have
higher ROS production and decreased
mitochondrial respiratory function that
cells in normoxic conditions
Isolated culture and intact organs
Hyperoxia post-resuscitation vs. survival from CA
Kilgannon et al. JAMA2010; 03(21):2165-2171
6,326 ICU patients from 120 US
hospitals from 2001-5
% of
cases
Mortality
Hyperoxia 18%
63%
[60%, 66%)
Normoxia 63%
45%
[43%, 48%]
Hypoxia 19%
57%
[56%, 59%]
Oxygenation Post ROSC
2010 AHA Guideline
Avoid unnecessary hyperoxia
Harms post ischemic neurons by
causing excessive oxidative stress
in early stages of reperfusion
FiO2 adjustments
Maintain O
2
saturation >94% and
<100%
Therapeutic Hypothermia
Management Issues
Induced Hypothermia (32-34 C)
The Hypothermiaafter CardiacArrest StudyGroup
NEngl J Med2002; 346: 549-556
7 European EDs
275 VT/VF pts with ROSC
Cooled to 32-34 C using an external
cooling device +/- ice packs for 24 h
Sedated with midazolam and fentanyl,
paralysed with pancuronium
0%
20%
40%
60%
80%
100%
Good Neuro Recovery Survival
Control Hypothermia
Induced Hypothermia (33 C)
Bernard SA et al. N Engl J Med 2002; 346:557-63
Australian study
73 OHCA pts with ROSC
Cooled to 33 C for 12 h
26%
49%
0%
20%
40%
60%
80%
100%
Survival
Control Hypothermia
Targeted temperature management (TTM) trial
Nielsen et al. N Engl J Med epub Nov 2013
950 patients randomized 2010-13
36 hospitals, 10 countries
Europe and Australia
Assess benefit/harms of a
targeted temperature
management at 33 vs 36C
Primary outcome: Survival
Secondary: mortality and poor
neurological function at 180 days
Cerebral Performance Category
Modified Rankin Scale
Page 5
Inclusion criteria
Out-of-hospital cardiac
arrest
Adult (18 years and over)
Presumed cardiac cause
All initial rhythms
Unconscious (GCS< 8)
Stable after ROSC
Patient selection
Exclusion criteria
Unwitnessed arrest with
initial rhythm asystole
>240 minutes from ROSC
Body temperature below
30C
Known or suspected
intracranial hemorrhage
and stroke
Design and timeline
Temperature intervention 36 hours
All patients sedated and ventilated minimum 36 hours
Feed-back controlled cooling devices in all patients
Intravascular or surface devices
Intervention
Inclusion 240 min
ROSC
Prognostication Half year follow up
ICU, hospital discharge
72 hours 36 h 180 days 956 d
Baseline characteristics
33 C 36 C
No. 473 466
Age
Male sex
64+/-12
83 %
64+/-13
79 %
Arrest in place of
residence
Arrest in public place
Bystander witnessed
Bystander CPR
Shockable rhythm
52 %
42 %
89 %
73 %
79 %
55 %
40 %
90 %
73 %
81 %
Arrest to ROSC (min) 25 [18-40] 25 [16-40]
Circulatory shock on adm.
Lactate mmol/L
15 %
6.74.5
14 %
6.74.5
ST-elevation infarction 40 % 42 %
GCS 3 [3-4] 3 [3-4]
Temperature profile
Mean 2SD
P<0.0001
Hours
Celcius
Outcomes
Outcome TTM33 TTM36 HR or RR (95% CI) P Value
PRIMARY OUTCOME
Mortality at the end of trial
Dead no./total no. (%) 235/473 (50) 225/466 (48) HR=1.06 (0.89-1.28) 0.51
SECONDARYOUTCOMES
Neurological function at
follow-up
CPC 3-5no./total no. (%)
mRS 4-6no./total no. (%)
Serious adverseevents
Any eventno./total no. (%)
252/469 (54)
245/469 (52)
439/472 (93)
242/464 (52)
239/464 (52)
417/464 (90)
RR=1.02 (0.88-1.16)
RR=1.01 (0.89-1.14)
RR=1.03 (1.00-1.08)
0.78
0.87
0.09
100% follow-up
99% follow-up
Subgroups
Prehospital initiation of therapeutic
hypothermia post-ROSC
Pilot Randomized Trial of Prehospital Induction of Hypothermia in
OOH-CA with Rapid Infusion of 2L of 4C Saline
Kimet. al. Circ 2007;115:3064-3070
p= .15
p= .13
p= ns
N= 125
No effect on CVP
Trend to systolic BP
No clinical or echo
evidence for volume
overload
Mean temp change= -1.2 C
Prehospital Induction of Hypothermia in OOH-CA due to VF with Rapid
Infusion of 2L Ringers Lactate at 4C Started After ROSC
Bernard et. al. Circ 2010;122:737-42
p= ns
N= 234
Immediately post ROSC
Midazolam 1-5mg and pancuronium 12mg
2L ice-cold Hartmanns via peripheral IV
Tympanic temperature
In the ED:
Further 1-2L cold Hartmanns (40mL/kg)
Conventional cooling
33C for 24 hours
All cooled at hospital
Terminated early because of futility
Page 6
Randomized Trial of Prehospital Induction of Hypothermia in
OOH-CA with Rapid Infusion of 4C Saline
Kimet. al. JAMA. Epub 2013 Nov 17
Mean temp change NS vs control
VF= -1.1 C
Non-VF= -1.2 C
N= 1,359
Median times from 911 call
to ROSC = 25-30 min
Functional Outcome
Assessment
Cognitive Deficits at Discharge in Cardiac Arrest
Survivors Treated with Therapeutic Hypothermia
Mary Ann Peberdy, Michelle R. Gossip, Charlotte S. Roberts, Sharon Bednar, Michael C. Kurz,
Renee D. Reid, Harinder Dhindsa, Joseph P. Ornato. AHAReSS 2013.
306 consecutive patients treated with
TH at VCU (10/08-4/13)
Survival= 51%
Of the 155 survivors, 60 (39%) were
tested with RBANS within 2 days of
discharge.
Reasons for not testing:
59 (38%) could not perform test
due to readily identifiable
neurocognitive deficits
21 (13%) were discharged prior to
testing
15 (10%) refused
Cognitive Deficits at Discharge in Cardiac Arrest
Survivors Treated with Therapeutic Hypothermia
Mary Ann Peberdy, Michelle R. Gossip, Charlotte S. Roberts, Sharon Bednar, Michael C. Kurz,
Renee D. Reid, Harinder Dhindsa, Joseph P. Ornato. AHAReSS 2013.
N= 155 survivors
97% of patients tested were CPC 1-2 and all were MRS <3 at discharge
78% male
95% witnessed
85% VF initial documented CA rhythm
Survival= 51%
Language
Visuospatial
Construction Attention
Immediate
Memory
Delayed
Memory RBANS Total
Reference
normal
100 100 100 100 100 100
Mean
[95%CI]
86.6
[84.4,88.8]
86.4
[79.4,93.5]
92.6
[86.7,98.5]
80.0
[74.4,85.6]
74.4
[67.9,81.0]
77.8
[73.3,82.4]
p .0001 .0001 .001 .0001 .0001 .0001
Next generation technology for protecting
the brain during and after resuscitation
External Head/Neck Cooling
Callaway C et al. Resuscitation 2002;52:159-65
27 OOH-CA pts
randomized to
usual care vs.
ice bags on head
& neck during
resuscitation
Monitored
nasopharyngeal
& esophageal
temp
Selective Brain Cooling
Rhinochill
Non-invasive
Intranasal PFC spray delivered
through nasal prongs
Can be initiated early
Ambulance or ED
Very rapid cooling
Upper airways designed for
heat exchange
Preferential brain cooling
Brain-core gradient
Intra-arrest transnasal cooling
Castren et al. Circulation 2010;122(7):729-36
194 out-of-hospital cardiac arrest
patients
15 sites, 5 European countries
Pts randomized to prehospital
nasal cooling or no prehospital
nasal cooling
Standard therapeutic hypothermia
used after hospital arrival
Transnasal cooling with dehumidified
high flow air
David Huberdeau
Page 7
Summary
Discussed controversial issues & latest advances in
CPR technique and sequencing
Review the evidence & ongoing studies on whether
ACLS drugs are of value during resuscitation
Discussed the controversy over hyperoxygenating
patients post-ROSC
Discussed the evolving science regarding the
prehospital use, optimal duration, depth, and target
for cooling in therapeutic hypothermia
Reviewed next generation technology for protecting
the brain during and after resuscitation