Marc M. Grossman MD FACEP Vol. Asst. Professor of Emergency Medicine and Neurology University of Miami-Miller School of MedicineJackson Memorial Hospital Emergency Services Medical Director, Coral Gables Fire-Rescue Associate Medical Director City of Miami Fire-Rescue
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
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% dischargeApproximately 2 to 5% with good neurological outcome
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
In the newsNew York Times:December 4, 2008 City PushesCooling Therapy for Cardiac ArrestBy ANEMONA HARTOCOLLIS
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
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.
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.
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
“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.
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 hospitalBernard SA, et al. N Engl J Med. 2002; 346:557-563.
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 completelydependent (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.
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 pancuroniumHACA Study Group. N Engl J Med. 2002; 346:557-563.
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
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!
“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
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 ROSCMouse model Abella Dog model HACA 2002 2004 Sterz 1991, Kuboyama 1993 Bernard 2002 60% survival Good neurologic outcome after Randomized clinical trails ROSC
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??
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
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.
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
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.
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
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
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.
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.
Intravascular Cooling Cooled saline flows within balloons Venous blood is cooled as it passes by each balloon Closed-loop system
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
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).
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
Tympanic Bladder Rectal Esophagus PA catheter
From Dr. Myron GinsbergModerate 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
CHILI:controlled Hypothermia in Large InfarctionCOAST-IIcooling in acute Stroke-IICombined Neuroprotective Modalities Coupled With Thrombolysis in AcuteIschemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia[SPOTRIAS]COOL AID ICooling Acute Ischemic Brain Damage - Safety and Feasibility StudyCOOL AID PilotCooling Acute Ischemic Brain Damage – PilotCOOL BRAIN-STROKECooling Helmet for Patients with Brain Ischemic and HemorrhagicInfarctionsHemicraniectomy and Moderate Hypothermia in Patients With Severe Ischemic StrokeICTuS-LIntravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke[SPOTRIAS]IHAST1Hypothermia and intracranial aneurysm surgery:part 1IHAST2Intraoperative Hypothermia for Aneurysm Surgery Trial, Part 2Mild Hypothermia in Acute IschemicStroke: Safety and Feasibility StudyNOCSSNordic Cooling Stroke StudyNOTHOTNormothermia and Stroke Outcome
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 expandingGuluma, et al Neurocrit. Care, 2008;8(1):42-7
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
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
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
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
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
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
“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”
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
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
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