Transcript Introdcution to Therapeutic Hypothermia

Introduction to Temperature
Therapy and Cooling
Temperature Therapy
Perspectives on Cooling
• Vital sign
• Maslov’s hierarchy of needs - shelter
• Nature’s design-metabolic protection
– Hibernation- Self protection mechanism
– Animals seek cool environment when ischemic
• Intuitive-”Cooling prevents spoilage”
• Learned-”Ice on injuries reduces swelling and tissue
damage”
• Physiological and biochemical rationale
– Tissue metabolic rates decrease as body temperature
decreases
Levels of Hypothermia-°C
>37.5=Hyperthermia
37.5 = Vasodilatation
36.6-37.5=Normothermia
36.5 = Vasoconstriction
34-36.5=Mild hypothermia
35.5 = Shivering
28-33.5=Moderate hypothermia
17-27.5=Deep hypothermia
4-16.5=Profound hypothermia
Temperature Therapy
• Historically, limited to temperature preservation, i.e.
warming in surgery, shock, etc.
• Investigation of cooling as a therapy limited by body’s
complex thermoregulatory mechanisms
– Core vs. peripheral dynamics
– Tolerance to change varies significantly individual to
individual
– Inability to cool with any precision and predictability
– Requirement to paralyze/anesthetize patient to
overcome thermoregulatory responses
– Significant complications that occur below 28°C
The Thermoregulatory System
Anterior Hypothalamus
Sweating
37 C
Heat loss
protection
Skin
Deep
Tissues
36 C
Spinal Cord
Brain (nonhypothalamic)
Vasodilation
Vasoconstriction
Thermogenesis
Thermogenesis
35 C
Nonshivering
Shivering
Techniques to Induce
Hypothermia
• Surface cooling techniques
– Slow and imprecise
– Cumbersome
– Limited in depth with non-paralyzed patient
• Lavage
– Moderately invasive and uncomfortable
– Slow and imprecise
• IV infusions
– Limited volumetric capacity
• Cardiopulmonary bypass
– Invasive and resource intensive
Cooling as a Therapy
• Despite challenges, long history of clinical and research
investigation
• 1940 - Neurosurgeon Temple Fay reported on first whole
body cooling*
• 1950 – Bigelow and Shumway published on hypothermia
as a cardioprotective agent that is the foundation for
today’s modern CPB technique**
• Transplant surgeons and cell physiologists routinely use
cooling to preserve cells and tissues
• Cooling is gold standard in many cardiac surgery and
neurosurgery procedures
* NY State J. Med 1940; 40: 1351-54
** Ann Surg 1950; 132: 849
Cooling as Therapy
Background
• Extensive research and evidence of the beneficial
effects and mechanisms of cooling
– Pre-clinical evidence of mechanisms, basic science
– Clinical trials evidencing the clinical benefits of cooling
• Despite current technical challenges of cooling,
several recently published clinical studies
demonstrate the benefits of cooling in:
– Cardiac Arrest*
– Stroke**
* NEJM 2002; 345: 549-56, NEJM 2002; 346: 557-63
** Stroke 2002; 32: 1847-54
Cooling as Therapy In
Cardiac Arrest Trial Results
• Two independent studies utilized surface cooling on intubated,
paralyzed patients vs. standard of care
• Multi-center, prospective, randomized trial in Australia*
– 77 pts: 43 hypothermia, 34 control
– 33°C x 12 hours following resuscitation from cardiac arrest
– Good neurologic outcome : 49% of cooled, 26% of controls
(p=.046)
• Multi-center, prospective, randomized trial in Europe **
– 275 pts: 137 hypothermia, 138 control
– 32°C to 34°C x 24 hours
– Good neurologic outcome in: 55% of cooled, 39% of controls
(p=.009)
– Mortality 41% in cooled vs 55% control, P=.02
* NEJM 2002; 346: 557-63
** NEJM 2002; 345: 549-56
Hypothermia in Malignant Stroke*
• Study Design
– Single center trial of mild cooling
– 25 patients with severe MCA strokes and increased ICP
– Cooling via surface cooling, cool infusions and cold
washing
– Cooling to 33°C within 14 hours after stroke, for 48 - 72
hours
• Results
– Decreased ICP with mortality of 44%, as compared to 80%
in historical controls
– Concluded that moderate hypothermia in the treatment of
severe cerebral ischemia is not associated with severe side
effects and may help control critically elevated ICP values
and improve clinical outcome in these patients
* Stroke 1998;29: 2461-2466
Hypothermia in Head Trauma
• Single center, prospective, randomized trial*
– 82 patients (40 - hypothermia to 33°C x 24 hrs)
– Improved outcome at 3 and 6 months in pts with initial
Glasgow Coma Scale score 5 - 7
• Multicenter, prospective, randomized trial **
– 392 pts (199 - hypothermia to 33°C x 48 hrs)
– Overall results negative
– Positive results in patients < 45 years who were
normovolemic
* NEJM 1997; 336: 540-6
** NEJM 2001; 344: 556-63
Surface Cooling Limitations
• Surface cooling used in
COOL AID* feasibility trial
demonstrated limitations of
surface cooling
• Target temperature of 32°C
• Actual temperatures reached
as low as 28°C
• Wide range in actual
temperatures and slow
cooling times
• Intensive cooling regime
including blankets, alcohol
wipes with paralyzed and
intubated patients
* Stroke 2001; 32: 1847-54
Target
Temperature
Endovascular Temperature
Therapy-Goals
 Safe
 Rapid cooling to target therapeutic levels in
ischemic tissues
 Precise cooling, maintenance, and re-warming
capabilities
 Minimally invasive, venous catheter-based method
 Comfortably cool awake patients
 Ease of use in a variety of locations, ICU, CCU, ER,
etc.
 Minimize resource intensity
 Minimal hemodynamic effects
TM
Endovascular Temperature
Therapy System
•Advanced heat exchange
technology
• System Components:
o Controller
o Heat exchange cassette
o Heat exchange catheter
o Temperature sensor
• FDA 510(k) clearance in
June of 2002 for use in
cardiac surgery patients to
achieve and/or maintain
normothermia
TM
Controller
•Easy to use graphical interface facilitates
system set-up and entry of cooling/warming
parameters
•Rapid cooling/warming capability with
precise control (+/-0.3°C)
•Integrated temperature feedback loop
automatically adjusts rate of patient
cooling/warming to targets specified by
operator
•Redundant safety systems with both audible
and visible alarms
•Self diagnosing, provides user-friendly
trouble shooting directions
TM
Catheter
• Delivered through
standard 10Fr sheath
• Expands to 27Fr when
inflated
• 25 cm long
heat exchanger
• Central lumen
for OTW
placement
• Helical multi-lumen
construction
maximizes surface
area for heat exchange
• Surface treatment to
minimize thrombogenicity
TM
Cassette
• Cools or warms circulating saline via
surface contact with cold/warm plates
in the controller
• Catheter pre-attached to cassette, no
assembly required
• Insulated foam lines reduce heat loss
• All in one design facilitates rapid setup and therapy initiation
•Cassette is easily removed from
controller to facilitate patient transfer
Shivering Management
Optimal Endovascular Therapy is dependent on
successfully managing three interdependent factors
•Buspirone and
Meperidine to reduce
shivering threshold
•Use of warm air blanket
to “fool” skin receptors
•Rate of core cooling and
maintenance
Skin Sensor
Drug-Brain
Management
Threshold
Endovascular
Temperature
Cooling the Awake Patient
Treatment Procedure
•
•
•
•
•
•
•
•
Administer Buspirone and Meperidine
Prepare System
Place catheter and temperature sensor
Initiate cooling to target of 33°C
Place warming blanket
Maintain at 33°C for prescribed duration
Re-warm to normothermia at controlled rate
Remove catheter and warming blanket
Clinical Trials of Cooling
• Ongoing or completed trials
– AMI (Radiant Medical - Endovascular)
– Ischemic Stroke (Radiant Medical -Endovascular)
– Hemorrhagic Stroke (Endovascular)
– Cardiac Arrest (Surface)
– Aneurysm Surgery (Endovascular & Surface)
– Brain Injury (Surface)