Newsweek July 2007

New York Times Dec 2008

Historical Perspective of HypothermiaHypothermia for

clinical purposes has ancient roots, used by Egyptians, Greeks, and Romans

Hippocrates advocated packing wounded patients in snow and ice to reduce hemorrhage

1950’s Hypothermia was utilized for intracranial aneurysm clipping and for cardiac surgery during circulatory arrest

1960’s Clinical trials with hypothermia (30 degrees Celsius or lower) were discontinued because of the side effects, uncertain benefits, and management problems

1980’s Animal studies showed benefits of mild (32-35 degrees Celsius) hypothermia rather than moderate or deep hypothermia (less severe side effects)

2002 ILCOR (International Liaison Committee on Resuscitation)

2005 AHA guidelines for Post Resuscitation Induced Hypothermia

Epidemiology of Cardiac ArrestApproximately

450,000 people experience Sudden Cardiac Arrest (SCD) every year

95% of patients that have experienced SCD died before they reach the hospital

The StudiesThe Studies-1. Bernard SA, Gray TW Treatment of comatose survivors of

out-of-hospital cardiacarrest with induced hypothermia NEJM 2002;346:557-563,

AustraliaResults: 49% vs 26%, hypo vs normo, had a “good outcome” - as defined by discharge to home or rehab2. Hypothermia After Cardiac Arrest Study Group. Mild

therapeutic hypothermia to improve the neurologic outcome after cardiac arrest NEJM

2002;346:549-556AustriaResults: 55% vs 39%, hypo vs normo, had a CPC-cerebral

performance category score of “good recovery” or “moderate disability”

Effect of Hyperthermia on Prognosis After Acute Ischemic Stroke

Methods—Data of 5305 patients in acute stroke trials from the Virtual International Stroke Trials Archive (VISTA) data Hyperthermia was defined as temperature 37.2°C

Conclusions—Hyperthermia, in acute ischemic stroke, is associated with a poor clinical outcome. The later the hyperthermia occurs within the first week, the worse the prognosis. Severity of stroke and inflammation are important determinants of hyperthermia after ischemic stroke. In patients with acute ischemic stroke, aggressive measures to prevent and treat hyperthermia could improve the clinical outcomes. (Stroke. 2009;40:3051-3059.)

PathophysiologyBrain loses oxygen stores within 20 secondsDamage starts 4-6 minutes after the heart

stopsGlucose and adenosine triphosphate stores

deplete (brain energy)Membrane depolarizationCalcium influxesGlutamine is releasedAcidosis and edema develop

Ischemia may persist for several hours after resuscitation (re-perfusion injury)

CardiovascularBradycardiaSlight increase in

blood Pressure (10mmHG)

Mild arrhythmias Increased PR intervalIncreased QT intervalWidened QRS

Increased Systemic Vascular Resistance

Increased Central Venous Pressure

Decreased Cardiac Output

Hematologic

ThrombocytopeniaImpaired platelet

functionLeukopeniaImpaired Leukocyte

functionIncreased PT/PTT

Gastrointestinal

Impaired Bowel Function

Decreased GI motility/ Ileus

Mild Pancreatitis (increased amylase)

Increased liver enzymes

Pharmacokinetics

Altered clearance of medicationsClearance is slowed

having a prolonged effect

Keep this in mind when re-warming.

GeneralBody attempts to

maintain homeostasisShiveringPeripheral

vasoconstrictionDecreased

circulation to skin

MetabolismIncreased fat

metabolism with increased production of glycerol, free fatty acids, ketonic acids, lactate

Metabolic acidosisDecreased oxygen

consumptionDecrease CO2

production

NeurologicDecreased metabolic rate 5-7 % for each 1

degree CDecreased Cerebral Blood Flow

(vasoconstriction)Decreased Magnesium- associated with

worse outcomes. Maycause Cerebral and Coronary

Vasoconstriction

Endocrine

Increased epinephrine, Nor epinephrine, and Cortisol levels

Hyperglycemia due to decreased insulin sensitivity and decreased insulin levels

Renal

DiuresisRenal Tubular

DysfunctionElectrolyte loss (K,

MG, Ca, Phos)

Mechanics of CoolingPassive Cooling

Ineffective have to wait on temperature to decrease to 33◦ Celsius

Active CoolingConvection

Air Cooling Blanket Therma cool Bair Hugger

Conduction Ice packs Cold Blankets

Infusion Cold NS infusion (2L

over 4 hours)

Exclusion Criteria• CPR for more than 45 minutes• Comatose or vegetative state prior to cardiac arrest• Evidence of hypotension (MAP < 60) for more than 30minutes after ROSC and prior to initiation of hypothermia• Terminal illness that preceded the arrest (life

expectancy < 1year)• Trauma• Temperature <34°C• Inability to intubate patient• Appearance of the gravid abdomen• Active bleeding/known pre existing coagulopathy (Note:Thrombolytic therapy does not preclude the use ofhypothermia)

Inclusion Criteria• Non-Traumatic cardiac arrest with return of spontaneouscirculation (ROSC) but remains unconscious• Patient > 16 years of age• Initial temperature > 34° C (93.2 °F)• Patient remains comatose (no purposeful response to pain)• Patient must be intubated to initiate protocol.• If patient meets other criteria for induced hypothermia and isnot intubated, then intubate according to protocol beforeinduced cooling.• If unable to intubate DO NOT initiate induced hypothermia.• Initiated within 3 hours of cardiac arrest• If there is loss of spontaneous circulation after cooling isinitiated, discontinue cooling and initiate appropriate protocol.

MonitoringABG’s every 8 hours.

(temperature adjusted)

Art line monitor B/P closely

SedationMAP greater than 80

mmHgCardiac Rhythm

Assess frequency of arrhythmias

Prolonged QT interval

Monitor Lytes every 8 hours

12 Lead ECG every 8 hours

Complications of HypothermiaPneumonia RiskVentilator DependencyDecreased WBC / BM

SuppressionDecreased Inflammatory

cytokinesElevated Glucose

Miscellaneous ComplicationsDoes NOT significantly increase metabolic

acidosisor Lactate levelsWill often cause mild HYPOTENSION, use

Pressorsto maintain MAP > 80 for cerebral perfusion

(90 – 100)Drug Metabolism slowed significantly(Propofol / Fentanyl / Verapamil / Propanolol)

ShiveringIncreases O2 Consumption between 40 – 100%Shivering responses occur primarily between 30 – 35

CSedation and anesthesia to halt shivering also

increasePeripheral Blood FlowIf you paralyze, you can’t screen for seizuresBuspirone (Buspar) 20mg PO q 8hrs / hold for SCr >

1.7Meperidine (Demerol) 25 – 50mg IV q 4 hrs prnUse Paralytics as second line

The Future is in Our Hands