Cardiac Arrest, Hypothermia and Resuscitation Science

Lecture 3: Cooling the body to save the heart and brain: Therapeutic hypothermia after cardiac arrest
Benjamin S. Abella, MD MPhil
Clinical Research Director Center for Resuscitation Science Department of Emergency Medicine University of Pennsylvania

An introductory course for the educated lay public and health care providers

Coursera July 2012

When do people die from cardiac arrest?

The post-arrest problem

arrest % Surviving CPR ROSC

in-hospital arrest data

52% 18% hospital discharge

Time

Concept of REPERFUSION INJURY

Reperfusion injury

% Surviving

Damage observed after restoration of blood flow to ischemic tissues

Time

Reperfusion injury: clues from the laboratory

Heart cells (myocytes) grown in a petri dish

Can simulate cardiac arrest and resuscitation:

Bathe them in fluid without oxygen (cardiac arrest) Restore fluid with oxygen (resuscitation)

What will happen when you simulate ischemia and then reperfusion?

60

ischemia

Death during ischemia ??

Cell Death (%)

50
40

30 20
10 0

Death during reperfusion

2 Time

What actually happens:

Cell Death (%)

Can we do something here?

ischemia

Time

Vanden Hoek et al, AJP, 1996

What this means: imagine the following situation

Would you buy this car for $75,000 ?

One quirk: if you run out of gas,

And you then put gas in the car

What this means: imagine the following situation

KAH BOOM

What causes this problem?

free radicals

inflammation

mitochondria

Reperfusion injury: how it happens

(lack of blood flow)

Ischemia

(return of blood flow)

Reperfusion

energy processing reactive oxygen dysfunction species (ROS) inflammatory cascades hypothermia

blood vessel instability cell death brain swelling

Cardiac arrest epidemiology in the US

EGYPT: In the time of the Pharaohs

The remarkable history of therapeutic hypothermia

Medicine in ancient Egypt

Hesi Re, Physician and scribe 2650 BCE

Imhotep, the god of healing

Ancient Medicine bottle

Sekhmet, goddess of disease

Medicine in ancient Egypt

Ancient Egyptians documented the use of hypothermia for: Pain control Fever Ice stored in straw, transported Long distances or made in Egyptian winters

Cardiac arrest epidemiology in the US

KOS: Island home to the Hippocratic tradition

Medicine in ancient Greece

Medicine in ancient Greece

Hippocrates noted that injuries (traumatic wounds) often did better when packed in ice or cooled No shortage of experimental subjects: constant skirmishing of Greek city states

Cardiac arrest epidemiology in the US

France: The Age of Empire

Hypothermia in the modern era

Baron Larrey: medical innovator

Baron Larrey (1766-1842) Chief battlefield surgeon under Napoleon

Developed important military medicine innovations:

The Flying Ambulance Caring for enemies (Prussians, seen here)

Baron Larrey observes hypothermia in action

Cold acts on the living parts [which] may remain in [a] state of asphyxia without losing their life (1814)

The first study of hypothermia in cardiac arrest

Benson DW, Williams GR Jr, Spencer FC, Yates AJ. The use of hypothermia after cardiac arrest. Anesth Analg 1959; 38: 423-8.
60 50 40
% 30

Comatose survivors Asystole or VF 31-32C Cooling until neurologic recovery (3 h to 8 days) water-filled blanket

20 10 0 Favorable neurologic recovery

Hypothermia (n=12) Normothermia (n=7)

The father of the science of hypothermia

Peter Safar, MD (1924-2003)

Anesthesia training at U Penn Worked in Pittsburgh

Father of CPR AND also developed hypothermia as a science

The father of the science of hypothermia