“Cool It”: Therapeutic Hypothermia for Recovery of Neurologic Function in

High Risk Patients Following Cardiac Arrest

Leah A. Swanson, Kalie M. Edelstein, William M. Parham, Jon S. Hokanson, Richard F. Shronts, Barbara T. Unger, Wendy B. George,

Ivan J. Chavez, Timothy D. Henry, Michael R. Mooney

Minneapolis Heart Institute FoundationAbbott Northwestern Hospital

March 29, 2009

Leah Swanson

The following relationships exist related to this presentation:

No relationships to disclose

Presenter Disclosure Information

Cardiac Arrest

• Out-of-hospital cardiac arrest (OOHCA) • 295,000 people annually in the US• 7.9% median survival rate• Anoxic encephalopathy and neurologic deficits• Therapeutic hypothermia (TH) clinical trials• ILCOR recommendation for TH after resuscitation

Lloyd-Jones D, Adams R, Carnethon M et al. Heart disease and stroke statistics-2009 update. Circulation 2009;119:e21-e181.

Hypothermia History

• 1950s - cardiac and neurologic surgeries

• Late 1950s - after cardiac arrest uncertain benefits

difficulties with implementation

• 1990s - studies in animal models histological benefits

functional benefits

• 2002 - randomized clinical trials of TH

Mechanisms

ischemia

glutamate release

oxygen-free radicals

calcium shifts

mitochondrial dysfunction

reperfusion

excitotoxicity

inflammatory cascades

cell death

blood brain barrier disruption & cerebral

edema

hypothermia

lower metabolic rate

less oxygen consumption

Geocadin RG, Koenig MA, Jia X et al. Management of brain injury after resuscitation from cardiac arrest. Neurol Clin. 2008;22:487-506.

HACA Study Group

• Randomized trial 2002 -hypothermia vs normothermia

• Methods Inclusion - OOHCA due to VF Exclusion – cardiogenic shock

• Hypothermia group 32°C - 34°C cooled for 24 hrs rewarming over 8 hrs

The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549-556.

3351assessed

3246ineligible

30not included

275enrolled

137hypothermia

138normothermia

HACA Study Group

• Neurologic outcome • Pittsburgh cerebral performance category scale

Cerebral Performance Category (CPC)

CPC 1 Good cerebral performance

CPC 2 Moderate cerebral disability

CPC 3 Severe cerebral disability

CPC 4 Coma or vegetative state

CPC 5 Brain death

Positive Outcomes

Negative Outcomes

HACA Study Outcomes

Hypothermia Normothermia

Survival 87/137 (64%) 69/138 (50%)

Favorable neurologic outcome 64/134 (47%) 42/135 (31%)

Survival and Neurologic Outcome at Discharge

“Cool It” Methods

Level 1 Heart Attack Program – STEMI transfers

“Cool It” Program - regional TH system - Feb 2006

Inclusion

non-traumatic OOHCA ROSC within 60 min unresponsive cardiogenic shock all ages

Exclusion

comatose before arrest DNR active bleeding

“Cool It” Methods

• Transfer patients standardized protocols

ice during transfer

• STEMI – immediate angiography and PCI

• Arctic Sun® TH device

• Target temperature 33°C for 24 hrs

• Rewarming at 0.5°C/hr

• Cerebral function at discharge

“Cool It” Patient Demographics

• 103 patients (Feb 2006-Oct 2008)

• 78 male, 25 female

• Average age 62 years

• 76% transferred

• 50% “Cool It” & STEMI

• 40% cardiogenic shock

Vtach Vfib

PEA

Asystole

“Cool It” Outcomes

All PatientsHACA

criteria (VT & VF)

Non-HACA criteria

(PEA, asystole, shock)

P Value

Total Number 103 52 51

Survival at Discharge

58 (56%) 38 (73%) 20 (39%) 0.0007

“Cool It” vs. HACA Survivors

0%

10%

20%

30%

40%

50%

60%

70%%

of

Su

rviv

ors

CPC 1 CPC 2 CPC 3 CPC 4Neurologic Outcome at Discharge

"Cool It"n =58HACAn=84

23.8%8.6%

Protocol Activation

• emergency department

• randomization

Methods Comparison

“Cool It”HACA

Protocol Activation

• field, referring hospital, in transfer

• education – early recognition & initiation

Cooling• no prehospital cooling• mattress cooling device• target temp• ice packs after 4 hrs

Cooling• target temp – as soon as

possible• ice packs in the field,

referring hospital, or in transfer

• Arctic Sun® cooling device

Shivering Prevention

• Pancuronium

• IV bolus every two hrs

Shivering Prevention

• Atracurium

• Infusion - TOF monitoring

“Cool It” vs. HACA Cooling

0

100

200

300

400

500

600

700

800

Tim

e (

min

ute

s)

HACA n=136 "Cool It" n=103

ROSC toTarget Temp

Arctic Sun toTarget Temp

ROSC toArctic Sun

720

309relative hazard

estimate = 1.25

(for 1 hr delay to TH)

Summary

• “Cool It” protocol applied TH to high risk patients cardiogenic shock PEA & asystole

• “Cool It” TH enhanced survival in HACA criteria patients

• “Cool It” TH preserved neurologic and functional status in a broader patient population

• “Cool It” survivors discharged with higher neurologic outcomes

• “Cool It” patients cooled to target temperature in less time

Conclusions• OOHCA is a significant health issue • TH is a markedly underutilized treatment• “Cool It” TH program

high survival rate high quality of life and cognitive and functional abilities

• “Cool It” TH - early & organized treatment standardized protocols outstate education rapid & early initiation of TH multidisciplinary team data collection and feedback

• TH can effectively be applied to a higher risk patient population than previously examined

• Neuroprotective adjunct to regional STEMI programs

Thank You!