1. Marc M. Grossman MD FACEP
Vol. Asst. Professor of Emergency Medicine
and Neurology
University of Miami-Miller School of Medicine
Jackson Memorial Hospital Emergency Services
Medical Director, Coral Gables Fire-Rescue
Associate Medical Director
City of Miami Fire-Rescue

2.  Describe advances in care of anoxic brain injuries
 Discuss the use of Induced Hypothermia in selected
patient populations
 Modalities
 Indications
 Contraindications
 Discuss the cooling by EMS and In-Hospital

3. Cardiac Arrest Outcomes
400,000 to 500,000 arrests / year in U.S.A
3/4 1/4
Out-of-hospital In-hospital
Return of
45% 55%
Spontaneous Circulation
Survival to hospital
2 to 8% 5 to 15%
discharge
Approximately 2 to 5% with good neurological outcome

5.  Unconscious adult patients with return of spontaneous circulation
(ROSC) after out-of hospital cardiac arrest should be cooled to 32°C to
34°C (89.6°F to 93.2°F) for 12 to 24 hours when the initial rhythm was
ventricular fibrillation (VF). Class IIa
 Similar therapy may be beneficial for patients with non-VF arrest out of
hospital or for in-hospital arrest. Class IIb
 AutoPulse IIb
 ResQPod IIa
Circulation. 2005;000:IV-84-IV-88

6. In the news
New York Times:
December 4, 2008 City Pushes
Cooling Therapy for Cardiac Arrest
By ANEMONA HARTOCOLLIS

7.  Ischemic Stroke
 Intracranial Hemorrhage
 Subarachnoid Hemorrhage
 Traumatic Brain Injury
 Spinal Cord Injury
 Anoxic Encephalopathy (Post Cardiac Arrest)
 Acute Myocardial Infarction
 Burns

9.  Maximum brain swelling is known to occur between
days 2 -5 after ischemia.
 Patients with uncontrolled elevated ICP have a
prolonged stay in ICU and worsened outcomes
 …Induced moderate hypothermia can decrease ICP &
may improve mortality in patients with severe
ischemic brain edema.
Schwab, Schwartz, Spranger, Keller, Bertram, Hacke, 1998

10.  Elevated temperatures after ischemia increase the
zone of injury around the penumbra (“Brain Fever”).
 Fever correlates with greater mortality and worse
outcome.
 Increased neurotransmitter release.
 Increased blood brain barrier permeability.
 Increased cellular brain damage.

11.  Decreasing Excitatory Aminoacid secretion.
 Downregulation of Glutamate receptors.
 Diminished production reactive Oxygen radicals.
 Reduced consumption of tissue antioxidants.
 Reduced inflammatory response.
 Lowering cerebral metabolic rate.
 Changes in cerebral blood flow.

12.  CNS
– For each 1°C decrease in temperature, the cerebral metabolic rate
decreases by 6–7%
– Hypothermia decreases intracranial pressure
– Hypothermia may act as an anticonvulsant
 Cardiovascular
• Decreases heart rate
 Decreases spontaneous depolarization of the cardiac pacemaker cells
 Prolongs action potential duration (of both the depolarization and
repolarization),
 Slows myocardial impulse conduction,
 Increases systemic vascular resistance
 Intense shivering increases metabolic rate and oxygen demand
 Need sedation and/or paralytic agents
 Stroke volume and mean arterial blood pressure are maintained
The electrocardiogram may show a notch on the downstroke of the
QRS complex (the Osbourne wave or J wave): present in 80% of
patients, all below 32º
Aslam AF, et al. American J Med. 2006; 119:297-301

15. “They’re not dead until they’re warm and dead”
 46 patients with deep hypothermia (core temperature < 28oC or 82.4oF)
– Mostly mountaineering accidents or suicide attempts
– 32 patients re-warmed with cardiopulmonary bypass with 15 long term survivors
• Average time to rewarming greater than 2 hours
– Average follow-up greater than 6 years ->No hypothermia related sequelae which
impaired quality of life
– Neurologic and neuropsychological defefits seen early had fully or almost
completely resolved (One patient with cerebral atrophy on MRI – possibly related)
• Conclusions: This clinical experience demonstrates that young, otherwise healthy
people can survive accidental deep hypothermia with no or minimal cerebral
impairment, even with prolonged circulatory arrest.
Walpoth BH, et al. N Engl J Med. 1997; 337:1500-1505.

18.  Rational:
Cold packs to head in the
– Cerebral ischemia may persist for several field and hospital
hours after resuscitation
– Hypothermia decreases cerebral oxygen Intubation and MV
demand Cold packs to torso in
 77 patients randomized to either hypothermia the field and hospital
vs standard care Midazolam/vecuronium in
– Initial cardiac rhythm of ventricular the hospital
fibrillation at the time of arrival of the Core temperature
monitored
ambulance
– Initiated by paramedics in the field continued Iced saline 4oC
in the hospital
Remove all clothing in
– 43 patients in hypothermia group (core the field
temperature 33o C, 91.5o F) within 2 hours of
Cold packs to limbs and
ROSC and maintained for 12 hours neck in hospital
Bernard SA, et al. N Engl J Med. 2002; 346:557-563.

19. Hypothermia Normothermia
(n=43) (n=34)
Normal or minimal disability (able to care for
15 (35%) 7 (21%)
self, discharged directly home)
Moderate disability (discharged to a
6 (14%) 2 (6%)
rehabilitation facility)
Severe disability, awake but completely
dependent (discharged to a long-term nursing 0 1 (3%)
facility)
Severe disability, unconscious (discharged to
0 1 (3%)
a long-term nursing facility)
Death 22 (51%) 23 (68%)
Bernard SA, et al. N Engl J Med. 2002; 346:557-563.

20.  Patients arriving to the ER with:
– Witnessed arrest, V-fib or pulseless
V-tach
– ROSC less than 60 minutes
 Patients randomized to either
hypothermia vs standard care
– Patients in hypothermia group (core
temperature 32 - 34o C) for 24 hours,
followed by passive rewarming for 8
hours
– External cooling device
– Ice packs if necessary
– IV midazolam, fentanyl and
pancuronium
HACA Study Group. N Engl J Med. 2002; 346:557-563.

21. Outcome Normothermia Hypothermia P value
Favorable Neuro Outcome 54/137 (39%) 75/136 (55%) 0.009
Death 76/138 (55%) 56/137 (41%) 0.02
Complication Normothermia Hypothermia
Bleeding 19% 26%
Pneumonia 29% 37%
Sepsis 7% 13%
Renal failure 10% 10%
Pulm edema 4% 7%
Seizures 8% 7%
Arrhythmias 32% 36%
HACA Study Group. N Engl J Med. 2002; 346:557-563.

22. Outcome
Vfib/ CPC 1 CPC 2 CPC 3 CPC 4 CPC 5
Total Moderate Severe Vegetative Death
Vtach Recovery Disability Disability State
Therapeutic 18/43 (41.9) 6/43 (13.9) 2/43 (4.7) 0/43 (0) 17/43 (39.5)
hypothermia
Standard 6/43 (14.0) 5/43 (11.6) 8/43 (18.6) 0/43 (0) 24/43 (55.8)
resuscitation
Outcome
Asystole/ CPC 1 CPC 2 CPC 3 CPC 4 CPC 5 Death
PEA Total Moderate Severe Vegetative
Recovery Disability Disability State
Therapeutic 2/12 0/12 0/12 0/12 10/12
hypothermia
Standard 0/11 0/11 1/11 0/11 10/11
resuscitation

23.  Induced Hypothermia after V-Fib Arrest: 6
 Beta-Blocker after Myocardial Infarction to prevent
sudden cardiac death: 42
 Primary prevention of stroke using a daily low dose
of aspirin for one year: 102
 Prevention of infection from dog bites using
antibiotics: 16

24. 2004
 265 Physicians surveyed from Emergency Medicine, Critical
Care and American Heart Association
 “Are you cooling cardiac arrest patients?”
 87% - “No. Have not started cooling patients”
WHY?
 49% “Not enough data”
 32% “Not incorporated into AHA ACLS protocol”
 28% “Cooling methods technically difficult or slow”
AHA Guidelines Eliminate 1 Major Excuses!

25.  “We are cooling” (35 sites)
 What method are you using to cool
 50% cooling blankets
 15% Ice packing
 13% Iced gastric lavage
 2% cooling mist
 2% cooling catheter (ONLY 1 site)
 17% other methods

27. When to start cooling?
Probably as soon as possible
ROSC
Cardiac
Arrest
0 1 2 3 4 5 6 7 8
Time (hours)
Intra-arrest Soon after ROSC
Pretty Soon after ROSC
Mouse model Abella Dog model
HACA 2002
2004 Sterz 1991, Kuboyama 1993
Bernard 2002
60% survival Good neurologic outcome after
Randomized clinical trails
ROSC

28. How deep to cool??
--34°C
Therapeutic Window?
--32°C
Too low may increase the occurrence of adverse
events such as arrhythmias or bleeding problems
or negate the benefits of cooling
Overcooling??

29.  Cardiac arrest with return of spontaneous circulation
(any initial rhythm)
 Men and Women age 18 years or older. Women of
childbearing age must have a negative pregnancy test
(must be documented on the chart)
 Coma after return of spontaneous circulation
(ROSC) (Coma is defined as: not following
commands, no speech, no eye opening, no purposeful
movements to noxious stimuli. Brainstem reflexes
and pathological/posturing movements are
permissible.)
 Endotracheal intubation with mechanical ventilation
 Blood pressure can be maintained at least 90 mm Hg
systolic either spontaneously or with fluid and
pressors

30.  Another reason to be comatose (e.g. head trauma, stroke, overt status
epilepticus) where benefits/risks of cooling are unknown.
 Pregnancy
 Temperature of <30°C after cardiac arrest
 Patients with a known bleeding diathesis, or with active ongoing
bleeding - hypothermia may impair the clotting system.
 No limit on duration of resuscitation effort; however “down time” of
less than 30 minutes most desirable
 Do not resuscitate (DNR) or Do not intubate (DNI) code status and
patient not intubated as part of resuscitation efforts
 Systemic infection/sepsis- hypothermia inhibits immune function and
is associated with an increased risk of infection
 Recent major surgery within 14 days - hypothermia may increase the
risk of infection and bleeding.

31. External Cooling
– Ice packs (0.9°C/hr)
– Water Immersion (9.7°C/hr)
– Cooling blankets (0.3–0.5°C/hr)
– External cooling equipment with
conductive surface pads (Arctic Sun)
(2-3°C in 90 minutes)
Internal Cooling
– Iced lavage (minimally effective)
– Iced IV saline or LR (1.6C over 25 mins )
– Intravascular catheter based cooling
equipment

34. Water Immersion Laboratory

35.  External cooling with cooling blankets or surface heat-exchange device and ice
Eligibility should be confirmed, and materials should be gathered.
 Obtain 2 cooling blankets and cables (one machine) to “sandwich” the patient. Each blanket should have a sheet covering it to protect the patient’s skin.
 Pack the patient in ice (groin, chest, axillae, and sides of neck); use additional measures as needed to bring the patient to a temperature between 32ºC and 34ºC. Avoid
packing ice on top of the chest, which may impair chest wall motion.
 Monitor vital signs and oxygen saturation and place the patient on a continuous cardiac monitor, with particular attention to arrhythmia detection and hypotension.
 Once a temperature below 34ºC is reached, remove ice bags, and the cooling blanket or heat-exchange device is used to maintain temperature between 32ºC and 34ºC.

36.  Patient temperature is to a
preset temperature by water
flowing through Arctic Sun
Energy Transfer Pads™
 Cools 2-3°C in 90 minutes
 Precise temperature control
minimizes overshoot
 Designed to mimic water
immersion
 Uses cooled water, but pads
resistant to leaking unlike
older water blanket systems

37.  Hydrogel is conductive w/ adhesive
surface, provides direct skin contact
 Thin film layer provides low
thermal resistance
 High velocity water flow transfers
energy
 No need to remove for
radiographic imaging even with
water flowing
– MRI
– CT Scan
– X-ray
– Cath lab
 Pads are latex free

38.  Celsius Control SystemTM (Innercool Therapies)
 Catheter incorporates a flexible temperature control element (TCE) that is
cooled or warmed with saline solution circulated in closed-loop.
 Placed in inferior vena cava & venous core blood is cooled/warmed as it
flows past the TCE back to the heart.
 Console receives feedback from intravascular sensor to achieve target
temperature.
 No fluid in infused into the patient.

39.  Coolguard system by Alsius.
 Currently in use by
Department of Neurosurgery
at UM/JMH
 Cooled saline flows within
balloons & venous blood is
cooled as it passes.
 Desired temperature & rate of
achievement set in control
panel.
 ICY catheter®
 Placed in IVC
 Multi-lumen
 MRI compatible
 Subclavian catheter available.

40. Intravascular Cooling
Cooled saline flows
within balloons
Venous blood is cooled
as it passes by each
balloon
Closed-loop system

41.  Cool down (QUICK!) :Time to target temperature is essential. Goal to
achieve desired temperature in < 6 hours. Aim for 2-4 hours. Animal
studies suggest peak in glutamate release around 1 hr after injury thus
early cooling probably better.
 Sedation
 Shivering Control
 Treat Underlying Cause (STEMI?)
 Close monitoring: Tight glycemic control, K, Mg, B/P
 Check for underlying Seizures (EEG, AED)
 Slow and Controlled Rewarming

42.  Drips for sedation (whatever you have and are
comfortable with)
 Demerol and skin counterwarming:
 For Stroke and the awake patient, oral buspirone (30
mg) and intravenous meperidine (0.4 mg/mL) have
been shown to act synergistically to lower the
shivering threshold from 35.7 C to 33.4 C while
producing only minimal sedation (Mokhtarani et al.,
2001; Doufas and Sessler, 2004).

44.  Most important: Spike in Intercranial Pressure, opposite from cooling phase
 This can Kill!
 Vasodilatation
– Avoid dehydration
 Potassium shifts from intracellular to extracellular (rises with re-warming)
– When to replace
 Rewarming
– Begin after target temp reached for 12 to 24 hours of total cooling
– Aim for 0.25-0.5°C per hour until normothermic
– Newer internal and external cooling devices have controlled re-warming
capability

45.  Tympanic
 Bladder
 Rectal
 Esophagus
 PA catheter

46. From Dr. Myron Ginsberg
Moderate therapeutic hypothermia represents one of the most solidly evidence-based neuroprotective
strategies currently available (Hemmen and Lyden, 2007). A large corpus of experimental studies
over the past 20 years has provided incontrovertible evidence that moderate hypothermia is
capable of conferring high-grade neuroprotection in focal and global cerebral ischemia by
impeding a host of deleterious metabolic and biochemical injury mechanisms, with a therapeutic
window appropriate for clinical application in ischemic stroke.
These clinical successes notwithstanding, the application of moderate therapeutic hypothermia to treat
patients with acute ischemic stroke has proceeded slowly. In part, this is attributable to (a) the
increased difficulty and complexity of patient
management (e.g., need for intensive care unit setting, sedation, shivering control, possible
intubation, cooling-device management); and (b) concerns regarding possible adverse events,
including pneumonia and (at lower temperatures) cardiac arrhythmias and coagulation
disturbances. .
Recent improvements in shivering management and advances in cooling technology, however, have
contributed to making therapeutic hypothermia in stroke patients more feasible at the present
time.
M.D. Ginsberg / Neuropharmacology 55 (2008) 363e389

47. CHILI:controlled Hypothermia in Large Infarction
COAST-IIcooling in acute Stroke-IICombined Neuroprotective Modalities Coupled With Thrombolysis in Acute
Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia[SPOTRIAS]
COOL AID ICooling Acute Ischemic Brain Damage - Safety and Feasibility Study
COOL AID PilotCooling Acute Ischemic Brain Damage – Pilot
COOL BRAIN-STROKECooling Helmet for Patients with Brain Ischemic and Hemorrhagic
InfarctionsHemicraniectomy and Moderate Hypothermia in Patients With Severe Ischemic Stroke
ICTuS-LIntravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke[SPOTRIAS]
IHAST1Hypothermia and intracranial aneurysm surgery:part 1
IHAST2Intraoperative Hypothermia for Aneurysm Surgery Trial, Part 2Mild Hypothermia in Acute Ischemic
Stroke: Safety and Feasibility Study
NOCSSNordic Cooling Stroke Study
NOTHOTNormothermia and Stroke Outcome

48.  RCT combines use of IV TH (Innercool) with IV-tPA
for stroke. Investigation to try to extend the window
for use of IV-tPA past 3 hours
 One recent small morphometric analysis from the
study shows that IV TH decreases acute post-
ischemic cerebral edema
 Trial ongoing and expanding
Guluma, et al Neurocrit. Care, 2008;8(1):42-7

52.  36 y/o woman, no PMH
 Had allergic reaction and had order in clinic for Benadryl iv
and epi im
 Epi given iv, pt went into v-fib arrest
 Found “seizing”, defib quickly
 BIBA w/ pulse, breathing, gcs=4, decorticate posturing,
minimal brain stem reflexes
 Cooling initiated within 30 minutes of arrival to ER, about 90
minutes post-arrest

53.  Initial temp: 38.1 degrees, ?aspiration pneumonia on cxr vs ards
 Cooled with IVNS 2L at 4 degrees, Arctic Sun pads applied
 About 4 hours to get to goal temp
 Question of adequate sedation and paralytics? Magnesium?
Counter warming
 No obvious shivering noted
 Echo shows ef=18%
 Pt critically ill for 7 days

54.  On day 8, pt awoke
 EF=50% (?stunned myocardium vs myocarditis)
 Extubated that day
 No neurologic deficit, does not remember what happened to
her
 Discharged 6 days later to home with close follow-up

55.  52 y/o woman, h/o htn only, witnessed arrest, cpr
and aed applied by co-workers
 ROSC, total downtime about 4 minutes
 On arrival, gcs=8, pt agitated
 Cooling protocol enacted, IVNS and Arctic Sun pads
 Goal temp reached in about 3 hours

56.  Pt found to have a left sided deficit and right MCA stroke by MRI
 Thrombolytic not given
 Pt remained comatose but agitated for about 12 days
 Calmed down and was weaned off vent on day 13 successfully
 Discharged on day 23 to rehab
 Pt seen by me 2 months later, only deficit is slight slurring of
speech, otherwise fully ambulatory, cognition intact and carrying
out ADLs, working again in a limited capacity

57.  26 year old female, s/p attempted hanging
 BIB-FR, cut down by PD, was in asystole, (+)ROSC
 Could not clear c-spine despite (-) CT Brain & Neck
 External Pads would require too much movement
and manipulation to apply and maintain
 Internal Cath started and patient cooled
 Minimal patient movement required, ideal situation
for cath cooling

60. “Unconscious adult patients with spontaneous
circulation after out-of-hospital VF cardiac arrest
should be cooled to 32-34oC. Cooling should be
started as soon as possible and continued for at least
12-24 hours.”
NolanJP, Deakin CD, Soar J, et al. European Resuscitation Council Guidelines for Resuscitation 2005 Section 4. Adult advanced life support.
Resuscitation 2005; 67 (Suppl 1): S39-S86.
5 Fire Rescue Departments in Dade County (Cities of Miami, Coral Gables, Key
Biscayne, Hialeah and Miami Beach) as well as FDNY and Seattle Fire Dept.
and several others are moving toward Induced Hypothermia in the field and
only bringing those patients to “Hypothermia Centers”

61.  JMH cooling for other indications for about 6 years
 In 2006, began to meet: ICU, ER, NSG, Neuro regarding cooling ROSC as per
AHA-ACLS Guidelines
 Took about a year to get a protocol together and start cooling, but very slow
progress
 In 2008, EMS interest in cooling took off, and grant to get coolers in every rescue
truck
 Put out request to all STEMI hospitals and others to begin cooling to be
considered Resuscitation Centers
 Some interest from many hospitals
 Gave some training to hospitals, they met with reps from 2 companies
 Started cooling October 2008, still gathering data
 Now have 8 facilities in Miami-Dade who cool and receive these patients
 May have 3 more on line before the end of the year
 Example of EMS driven advances in care for hospitals

62.  84 y/o F, asystole arrest, HD, CRF, HTN, downtime
8 minutes, ROSC, cooled, awoke on day 4, home via
rehab for vent-dep.
 56 y/o M, htn hx, down at store, defib AED by
CGPD, ROSC, cooled in field, cath 90%LAD, PTCA,
D/C to home
 47 y/o F h/o obesity, htn, dm, down in café, early
CPR, defib, ROSC, cooled and d/c to rehab then
home

65.  CLIFTON, G.L., MILLER, E.R. ET. AL. (2001). LACK OF EFFECT OF INDUCTION OF
HYPOTHERMIA AFTER ACUTE BRAIN INJURY. NEW ENGLAND JOURNAL OF MEDICINE,
344, 556-563.
 FRITZ, H.G.& BAUER, R. (2004). SECONDARY INJURIES IN BRAIN TRAUMA:EFFECTS OF
HYPOTHERMIA. JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY, 16(1), 43-52.
 MCILVOY, L.H. (2005). THE EFFECT OF HYPOTHERMIA AND HYPERTHERMIA ON ACUTE
BRAIN INJURY, AACN CLINICAL ISSUES, 16(4), 488-500.
 WRIGHT, J.E. (2005). THERAPEUTIC HYPOTHERMIA IN TRAUMATIC BRAIN INJURY.
CRITICAL CARE NURSING QUARTERLY, 28(2), 150-161.
 ZHI, D., ZHANG, S., & LIN, X. (2003). STUDY ON THERAPEUTIC MECHANISM AND
CLINICAL EFFECT OF MILD HYPOTHERMIA IN PATIENTS WITH SEVERE HEAD INJURY.
SURGICAL NEUROLOGY, 59, 381-5.
 HEMMEN TM, LYDEN PD (2007) NEW APPROACHES TO CLINICAL TRIALS IN
NEUROPROTECTION: INTRODUCTION INDUCED HYPOTHERMIA FOR ACUTE STROKE
STROKE 2007 FEB;38(2 SUPPL):794-9

66. Questions??
M.Grossman1@Miami.edu