# Presentation: 274534

## Post-Event Hypothermia

**Julie Swain M.D.**
**Cardiovascular Surgeon**
**Consultant to the FDA**

**Circ System Devices Advisory Panel**
**Sept 2004**

**DRAFT slides**

## Outline of Presentation

**Post-event hypothermia in MI**
**Post-event hypothermia in head trauma**
**Post-event hypothermia in resuscitation**
**ILCOR recommendations**
**Questions for panel**

- Swain

## 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**

- Swain

## COOL-MI Study Results

**% LV**
**Infarct**
**Size**

**N = 180**

**N = 177**

**p = N.S.**

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

- Swain

## 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

- Swain

## 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**

- Swain

## 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**

- Swain

## Brain Injury Outcome

**% of **
**Patients**
**Poor **
**Outcome**

**N = 193**

**N = 199**

**p = N.S.**

**p = N.S. for all secondary endpoints**

**57%**

**57%**

- Swain

## 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**

- Swain

## Post-Event HypothermiaCardiac 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]**

- Swain

## 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**

- Swain

## 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° |

- Swain

## Comparison of Cardiac Arrest Studies

|  | Australia | Europe
 |
| --- | --- | --- |
| Rewarming | Active | Passive |
| Adjunctive meds | Midazolam
Vercuronium | Midazolam
Fentanyl
pancuronium |

- Swain

## 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
 |
|  |  |  |

- Swain

## Comparison of Cardiac Arrest Studies

**% success**
**endpoint**

**{Australia}**

**{Europe}**

**p = .046**

**(***********risk ratio 1.40, CI 1.08 – 1.81)**

*******

- Swain

## Comparison of Cardiac Arrest Studies

**% mortality**

**{Australia}**

**{Europe}**

*******

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

**p = N.S.**

- Swain

## 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.**

- Swain

## 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**

- Swain

##  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?**

- Swain

**Notes:**
Talk about is  European extrapolable to US
We have lots of surface cooling devices, can labeling be added
2nd bullet talk about cardiac arrest