Post-Event HypothermiaPost-Event Hypothermia

Julie Swain M.D.

Cardiovascular SurgeonConsultant to the FDA

Circ System Devices Advisory PanelSept 2004

DRAFT slides

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Outline of Presentation

1. Post-event hypothermia in MI

2. Post-event hypothermia in head trauma

3. Post-event hypothermia in resuscitation

4. ILCOR recommendations

5. Questions for panel

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Post-Event Hypothermia in Myocardial Infarction

(Cool-MI Study)

• Data presented at TCT 2003(www.radiantmedical.com/download/TCT-ONeill.pdf)

• Prospective, randomized (cooling with IVC catheter vs normothermia during PCI)

• MI < 6 hrs, cool to 33°C for 3 hrs

• Quantitative Endpoint – infarct size at 30 days

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COOL-MI Study Results

13.8 % 14.1 %

0

10

20

30

control hypo T

% LVInfarctSize

N = 180 N = 177

p = N.S.

Data presented at TCT 2003(www.radiantmedical.com/download/TCT-ONeill.pdf

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COOL-MI Results

Complication Control

(n=180)

Hypo T (33°)

(n=177)

Death 2.2% 3.4%

Vascular/bleeding 15.6% 19.2%

DVT 0 1.7%

Shock 6.1% 12.4%

Pulm Edema 1.7% 3.4%

P = n.s. for all complications, not powered to assess MACE

Data presented at TCT 2003(www.radiantmedical.com/download/TCT-ONeill.pdf

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Post-Event Hypothermia in Brain Injury

(Clifton GL, et al. Lack of Effect of Induction of Hypothermia after Acute Brain Injury.  N Engl J Med 2001; 344: 556-63)

• Prospective, randomized, surface and GI cooling vs normothermia

• Injury < 6 hrs, cool to 33°C for 48 hrs• Endpoint – Glasgow Outcome Score at 6

months (functional independence with mild or moderate disability)

• Secondary endpoints of psychometric tests

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Secondary Endpoints in Brain Injury Trial (at 6 mos)

• Neurobehavioral Rating Scale – Revised• Disability Rating Scale• Galveston Orientation and Amnesia test• Selective Reminding Test• Rey-Osterrieth Complex Figure Test• Symbol Digit Modalities Test• Trail Making Test B• Controlled Oral Word Association Test• Grooved Pegboard Test

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Brain Injury Outcome

0

25

50

75

100

Control HypoT

% of PatientsPoor Outcome

N = 193 N = 199

p = N.S.

p = N.S. for all secondary endpoints

57% 57%

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Brain Injury Study Results

Complication Control

(n=193)

HypoT

(n=199)Critical Hypotension 3% 10%

Bradycardia w hypotension 4% 16% p = .04

% of hosp. days with complications

70% 78%

p = .01

p = .005

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Post-Event HypothermiaCardiac Arrest

• Bernard SA, et al.  Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia.  N Engl J Med 2002; 346:557-63 [Australia]

 • The Hypothermia After Cardiac Arrest Study

Group.  Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest.  N Engl J Med 2002; 346:549-56 [Europe]

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Comparison of Cardiac Arrest Studies

Location Australia Europe

# hypoT pts 43 136

Inclusion

Criteria

VF, return Spon Circ, coma, men>18 yrs, women >50 yrs

Witnessed arrest, VF, VT, cardiac origin, 18-75 yrs, 5-15 min to resuscitation by medical personnel, <60 min from arrest to restore circ ***

***91% of screened pts not eligible

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Comparison of Cardiac Arrest Studies

Australia Europe

When cooling started

In field Hospital admission

Cooling method Cold packs then ice packs

Air-cooled mattress, ice packs

Target Duration hypoT

12 hrs 24 hrs

Target Temp 33° 32-34°

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Comparison of Cardiac Arrest Studies

Australia Europe

Rewarming Active Passive

Adjunctive meds Midazolam

Vercuronium

Midazolam

Fentanyl

pancuronium

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Comparison of Cardiac Arrest Studies

Australia Europe

Primary

Endpoint

survival to hospital discharge with neuro function allowing home or rehabilitation

CPC good or moderate disability at 6 mos

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Comparison of Cardiac Arrest Studies

26%

49%

39%

55%

0

25

50

75

100

control hypo T control hypo T

% successendpoint

{Australia} {Europe}

p = .046

(***risk ratio 1.40, CI 1.08 – 1.81)

***

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Comparison of Cardiac Arrest Studies

68%

51% 55%

41%

0

25

50

75

100

control hypo T control hypo T

% mortality

{Australia}

{Europe}

***

(***risk ratio 0.74, CI .58 - .95)

p = N.S.

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ILCOR Recommendations(ILCOR Advisory Statement.  Therapeutic Hypothermia after

Cardiac Arrest.  Circulation 2003;108:18-21)

• Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours when the initial rhythm was ventricular fibrillation (VF).

• Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest.

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Safety Profile of Cooling Methods• Surface

– Cool air– Water cooling– Head and neck cooling

• GI lavage

• Endovascular– Extracorporeal Circulation

• Cardiopulmonary Bypass• Veno-venous• Arterial venous

– IVC catheters

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Summary

• Is post-event hypothermia the standard for treating out-of-hospital arrest patients in the U.S.?

• Is surface-induced hypothermia comparable to endovascular hypothermia in safety and efficacy?