In the Media Newsweek July 2007 New York Times Dec 2008

Historical Perspective of Hypothermia Hypothermia 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 Arrest Approximately 450,000 people experience Sudden Cardiac Arrest (SCD) every year 95% of patients that have experienced SCD died before they reach the hospital

The Studies The Studies- 1. Bernard SA, Gray TW Treatment of comatose survivors of out-of- hospital cardiac arrest with induced hypothermia NEJM 2002;346: , Australia Results: 49% vs 26%, hypo vs normo, had a “good outcome” - as defined by discharge to home or rehab 2. Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest NEJM 2002;346: Austria Results: 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: )

Pathophysiology Brain loses oxygen stores within 20 seconds Damage starts 4-6 minutes after the heart stops Glucose and adenosine triphosphate stores deplete (brain energy) Membrane depolarization Calcium influxes Glutamine is released Acidosis and edema develop Ischemia may persist for several hours after resuscitation (re-perfusion injury)

Cardiovascular Bradycardia Slight increase in blood Pressure (10mmHG) Mild arrhythmias Increased PR interval Increased QT interval Widened QRS Increased Systemic Vascular Resistance Increased Central Venous Pressure Decreased Cardiac Output

Hematologic Thrombocytopenia Impaired platelet function Leukopenia Impaired Leukocyte function Increased PT/PTT

Gastrointestinal Impaired Bowel Function Decreased GI motility/ Ileus Mild Pancreatitis (increased amylase) Increased liver enzymes

Pharmacokinetics Altered clearance of medications Clearance is slowed having a prolonged effect Keep this in mind when re-warming.

General Body attempts to maintain homeostasis Shivering Peripheral vasoconstriction Decreased circulation to skin

Metabolism Increased fat metabolism with increased production of glycerol, free fatty acids, ketonic acids, lactate Metabolic acidosis Decreased oxygen consumption Decrease CO2 production

Neurologic Decreased metabolic rate 5-7 % for each 1 degree C Decreased Cerebral Blood Flow (vasoconstriction) Decreased Magnesium- associated with worse outcomes. May cause Cerebral and Coronary Vasoconstriction

Endocrine Increased epinephrine, Nor epinephrine, and Cortisol levels Hyperglycemia due to decreased insulin sensitivity and decreased insulin levels

Renal Diuresis Renal Tubular Dysfunction Electrolyte loss (K, MG, Ca, Phos)

Mechanics of Cooling Passive Cooling Ineffective have to wait on temperature to decrease to 33 ◦ Celsius Active Cooling Convection 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 30 minutes after ROSC and prior to initiation of hypothermia Terminal illness that preceded the arrest (life expectancy < 1 year) 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 of hypothermia)

Inclusion Criteria Non-Traumatic cardiac arrest with return of spontaneous circulation (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 is not intubated, then intubate according to protocol before induced 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 is initiated, discontinue cooling and initiate appropriate protocol.

Monitoring ABG’s every 8 hours. (temperature adjusted) Art line monitor B/P closely Sedation MAP greater than 80 mmHg Cardiac Rhythm Assess frequency of arrhythmias Prolonged QT interval Monitor Lytes every 8 hours 12 Lead ECG every 8 hours

Complications of Hypothermia Pneumonia Risk Ventilator Dependency Decreased WBC / BM Suppression Decreased Inflammatory cytokines Elevated Glucose

Miscellaneous Complications Does NOT significantly increase metabolic acidosis or Lactate levels Will often cause mild HYPOTENSION, use Pressors to maintain MAP > 80 for cerebral perfusion (90 – 100) Drug Metabolism slowed significantly (Propofol / Fentanyl / Verapamil / Propanolol)

Shivering Increases O2 Consumption between 40 – 100% Shivering responses occur primarily between 30 – 35 C Sedation and anesthesia to halt shivering also increase Peripheral Blood Flow If you paralyze, you can’t screen for seizures Buspirone (Buspar) 20mg PO q 8hrs / hold for SCr > 1.7 Meperidine (Demerol) 25 – 50mg IV q 4 hrs prn Use Paralytics as second line

The Future is in Our Hands

Reality is many patients with functional organs but non-functional Brain