Post on 30-May-2020
Hypothermic forHypothermic for Cardiac ArrestCardiac ArrestThe Evidence BaseStephan A. Mayer, MDDirector Neuro-ICUDirector, Neuro ICUColumbia UniversityNew York, NY
DisclosuresDisclosures
• Columbia University– Clinical Trials Pilot Award
• Radiant Medical, Inc.– Scientific Advisory Boardy– Stock Options
• Medivance, Inc.– Research Grant– Research Grant– Stock Options
• Seacoast TechnologiesS i tifi Ad i B d– Scientific Advisory Board
PETER SAFAR1924-2003
“Father of CPR”
Pioneered Intensive Care Units
Conceptualized fHypothermia for
“Suspended Animation”
HYPOTHERMIA: Mechanisms of I h i N t tiIschemic Neuroprotection
• Profound reduction of active and basal cellular i tenergy requirements
• Reduced excitotoxic neurotransmitter release• Reduced oxygen free radical productionReduced oxygen free radical production• Improved BBB stability• Decreased “ischemic depolarizations” in the
bpenumbra• Protection against cytoskeletal proteolysis• Decreased neutrophil infiltrationDecreased neutrophil infiltration• Decreased cytokine and leukotriene production
The ChallengeThe Challenge
• Intensivists manipulate physiologyIntensivists manipulate physiology• We now have improved tools to
precisely control body (and brain)precisely control body (and brain) temperature
• As intensivists, we are obliged toAs intensivists, we are obliged to identify and maintain an optimal temperature in patients with acute p pbrain injury
Out-of-hospital cardiac arrest is common
350,000+ per year in US, p y One out of 5 out-of hospital deaths occurs as a
sudden cardiac arrest Overall survival in US / Western Europe is 5-
8% B ti t d l i By some estimates, good neurologic recovery
occurs in only 3% of out-of-hospital arrests “Best” EMS systems: Seattle 1998-2001 Best EMS systems: Seattle 1998-2001
• Overall survival to hospital discharge 17.5%• VF/VT: 34% survived (vs. 6% with other rhythms)
NEJM 2004; 351 (7): 632
Out-of-hospital cardiac arrestOut of hospital cardiac arrest• Factors (likely) influencing outcome:( y) g
– Duration of non-perfusing rhythm– Bystander CPR– AEDs / early defibrillation– Quality of CPR (adequate cardiac
t t)output)– Age
Th ti h th i– Therapeutic hypothermia
NEJM 2004; 351 (7): 632
Out-of-hospital cardiac arrestOut of hospital cardiac arrest• Factors (likely) influencing outcome:( y) g
– Duration of non-perfusing rhythm– Bystander CPR– AEDs / early defibrillation– Quality of CPR (adequate cardiac
t t)output)– Age
Th ti h th i– Therapeutic hypothermia
NEJM 2004; 351 (7): 632
Effect of early time to defibrillationEffect of early time to defibrillation
NEJM 2004; 351 (7): 632
Improving OOHCA OutcomesImproving OOHCA Outcomes
FDNY Medics 2002 2003 2004 2005 2006 2007# of arrests 1537 1636 1555 1688 1801
% VF 12.88% 13.99% 13.69% 12.26% 12.66%
ROSC - overall 15.81% 17.60% 15.31% 15.40% 16.49%
ROSC – nonVF 14.04% 16.13% 13.71% 14.04% 15.44%
ROSC – VF/VT 27.78% 26.64% 25.35% 25.12% 23.25%
Sustained ROSC 11.13% 12.78% 10.03% 11.32% 11.94%
Improving OOHCA OutcomesImproving OOHCA Outcomes
FDNY Medics 2002 2003 2004 2005 2006 2007# of arrests 1537 1636 1555 1688 1801 1735
% VF 12.88% 13.99% 13.69% 12.26% 12.66% 14.72%**
ROSC - overall 15.81% 17.60% 15.31% 15.40% 16.49% 23.69%**
ROSC – nonVF 14.04% 16.13% 13.71% 14.04% 15.44% 18.32%**
ROSC – VF/VT 27.78% 26.64% 25.35% 25.12% 23.25% 54.88%**
Sustained ROSC 11.13% 12.78% 10.03% 11.32% 11.94% n/a
NYC Project HypothermiaNYC Project Hypothermia
Phase #1: Beginning July 1 2008 allPhase #1: Beginning July 1, 2008, all OOHCA patients achieving ROSC in New York City will only beNew York City will only be transported to facilities actively employing therapeutic hypothermiaemploying therapeutic hypothermia.
Hypothermia: Techniques
LIFE RECOVERY SYSTEMS
Intravascular heat exchange catheter d i d f i ti i th j l
Heat exchange
designed for insertion in the jugular vein and combined centralvenous capabilities (multiple infusion g
3 infusion lumens
ports)
Inflow Outflow
COOINNERCOOL
MEDIVANCE ARCTIC ARCTIC
SUN
Polderman et al. Induction of hypothermia in patients with various types of neurologic injury with use of large volumes ofvarious types of neurologic injury with use of large volumes of ice-cold intravenous fluid. Crit Care Med 2005;33:2744
• 134 brain injured• 134 brain- injured patients
• In addition to surface cooling 30 ml/kg 36
37 Temp (�
cooling 30 ml/kg (mean 2.3 liters) of cold normal saline over 50 minutes 34
35
over 50 minutes• MAP increased 15
mm Hg• No CHF
32
33
• No CHF
30
31
Baseline 1 Hour 2 Hours
METHODS: Mild/Moderate H th i P t l (33° C)Hypothermia Protocol (33° C)
• Endotracheal intubation• Sedation:
– Meperidine 25-100 mg IVP q 2-4 HD d t idi 0 3 0 7 /k /h– Dexmedetomidine 0.3 – 0.7 µg/kg/hr
• Paralysis: Vecuronium 0.1 mg/kg PRN• Thermistors: bladder, rectal, esophagealThermistors: bladder, rectal, esophageal• Radial artery and internal jugular lines• Intraparenchymal ICP & temperature monitor• Insulin drip for BS >180 mg/dl• Hypokalemia <3.4 mEq/l replaced
11
Hemodynamic Support afterHemodynamic Support after Cardiac Arrest
Norepinephrine
708090
100Dobutamine
708090
100Volume Expansion
708090
100% pts% pts
010203040506070
010203040506070
010203040506070
00-6 hrs 6-24 hrs 24-48 hrs 0-6 hrs 6-24 hrs 24-48 hrs
00-6 hrs 6-24 hrs 24-48 hrs
HypothermiaNormothermiaNormothermia
Oddo M, Crit Care Med, 2006;34(7):1865
METHODS: Mild/Moderate H th i P t lHypothermia Protocol
• ABGs at room temp (alpha-stat) • Vasopressors to keep CPP >70 mm Hg• ICP >20 mm Hg treated per protocol• Feedings held x 48 hoursFeedings held x 48 hours• Cultures/antibiotics for work of device heat transfer (indicating
thermogenesis)• Passive controlled rewarming (0 25 to 0 3 °C / hr)• Passive controlled rewarming (0.25 to 0.3 C / hr)• Active cooling is maintained at 36.5°C thereafter for 24 hrs to
avoid “overshoot”
2
Volume 346:549-556 February 21 2002 Number 8Volume 346:549-556 February 21, 2002 Number 8
Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest
The Hypothermia after Cardiac Arrest Study Group
Volume 346:557-563 February 21, 2002 Number 8
Treatment of Comatose Survivors of Cardiac ArrestTreatment of Comatose Survivors of Cardiac Arrest with Induced Hypothermia
Stephen A. Bernard, MB, BS,.and others
European HACA TrialEuropean HACA Trial
• SUBJECTS: 273 patients with out-of-hospital p pVT/VF arrest– Ages 18-75– Initiation of CPR within 15 minutes– Interval from collapse to ROSC <60 mins
• INTERVENTION: 32 34°C for 24 hours• INTERVENTION: 32-34°C for 24 hours– Mean 8 hours from initiation of cooling to
temperature <34°Cp
HACA Study Group, NEJM, 2002
Kinetic Concepts Air Cooling Devicep g
• Cool air blanket initiated ~2 hours after ROSCCool air blanket initiated 2 hours after ROSC
• Target temp attained ~8 hours later
HACA: Rate of CoolingHACA: Rate of Cooling
HACA: Rate of CoolingHACA: Rate of Cooling
European HACA TrialEuropean HACA Trial
• OUTCOME MEASURE: SurvivalOUTCOME MEASURE: Survival with minimal or moderate disability at 6 monthsy– 55% hypothermic – 39% normothermic39% normothermic
• Risk ratio for good outcome 1.40(1 08-1 81)(1.08-1.81)
• Number needed to treat = 6HACA Study Group, NEJM, 2002
Absolute mortality ydifference of 14%
Relative mortality d ti f 26%reduction of 26%
AUSTRALIAN Hypothermia i lTrial
• SUBJECTS: 77 patients with out-of-hospital p pVT/VF arrest– No upper age limit
Comatose– Comatose– Refractory shock (MAP <90) excluded– Randomization according to date (odd-even)
• INTERVENTION: 32-34°C for 12 hours– Cooling started in the field using ice bags
within 2 hours of collapsewithin 2 hours of collapse– Cooling period 12 hours– Rewarming over 6 hours
Bernard et al, NEJM, 2002
35% 21%
International Task ForceInternational Task Force
• 2003 ILCOR meeting on hypothermia drecommends:
“Unconscious patients with spontaneous circulation after out of hospital arrest should be cooled to 32-34°C for 12-24 hours when the initial rhythm is ventricular fibrillation.”
AND“Such cooling may also be beneficial for other rhythms or in-hospital arrest.”
Nolan, JP, Resuscitation, 2003
Post Resuscitation CarePost Resuscitation Care
The “Second” T l tiTranslationFROM SCIENCE FROM SCIENCE TO DAILY TO DAILY PRACTICE
Therapeutic hypothermia utilization among physicians after cardiac arrest Raina M Merchant et al Crit Care Med 2006 34 1935cardiac arrest Raina M. Merchant, et al, Crit Care Med 2006;34;1935.
• Web-based survey of 2,248 physicians• USA: 74% have never cooled
• EU: 64% have never cooled
Have you ever? If not why not?
Out-of-hospital cooling by Emergency Physician (Markus Födisch, Bonn)y ( )
• Can “evidence-based • Swiss retrospective study: 14 medicine” be implemented outside of the multicenter RCT
bed MICU in “university hospital” medical center
• June 1999 – May 2002: the multicenter RCT environment?
• Does TH work in smaller
– 54 patients with OHCA• June 2002-December 2004:
– 55 patients with OHCA medical centers?
ptreated with TH
CCM 2006:34:1865
Improved OutcomesImproved Outcomes
Time from collapse to ROSC
Probability ofProbability of good
outcome
Duration of cardiac arrest predicts outcome (OR of good outcome for each additional 5 min: 0 53 95% CI: (OR of good outcome for each additional 5 min: 0.53, 95% CI:
0.37-0.72, p<0.001)Oddo et al, CCM 2007
Results VUMC
Preliminary evidence in patients with asystole/PEA…
Polderman KH et al. Induced hypothermia improves neurological outcome in asystolic patients with out-of hospital cardiac arrest. Circulation 2003; 108: IV-581 [abstract 2646]
Northern H th i N t kHypothermia Network www.scctg.orgwww.hypothermianetwork.com
• Six scandanavian countries
• >500 patients
• 64% VT/VF
• 28% PEA
• 8% Asystole
HypothermicHypothermic
Polderman KH. Lancet 2008; 371:1955-1969
City Pushes Cooling Therapy for Cardiac A tArrest
December 4 2008December 4, 2008
Chain of SurvivalChain of Survival
• VF / pulseless VT (AHA level 2A)– Pulseless electrical activity / asystole (HA level 2B)y y ( )
• Comatose• Absence of refractory post-resuscitation shock
D ti f di t 5 30 i t• Duration of cardiac arrest 5-30 minutes• Age ≤75 years
Getting Serious about Hypothermia for CA:Keys to ImplementationKeys to Implementation
Education and Knowledgeg
Champion
Team Building
Administration and Nursing
P t lProtocols
The New ParadigmThe New Paradigm
CPR CCRCPR CCR
Cardio-Pulmonary Resuscitation
Cardio-Cerebral ResuscitationResuscitation Resuscitation