Therapeutic Hypothermia After Cardiac Arrest Angelita Ramos, RN, BSN Michelle Margerum, RN, BSN Sonam Norbu, RN, BSN

Objectives Discuss cardiac arrest, therapeutic hypothermia (TH) Review goals of therapy Discuss guidelines of therapeutic hypothermia post- cardiac arrest, indications and contraindications Discuss clinical evidence for TH Discuss mechanism of action, pathophysiology of hypothermia post cardiac arrest Review cooling methods/procedure Review treatment protocols

Case Scenario TJ, a 65 year old African-American Male Hx CAD, CHF, DM-type 2, HTN, COPD Patient called 911 for SOB Witnessed cardiac arrest at the scene with initial rhythm VTach Defibrillated x2 with ROSC Intubated at the scene Total down time 15 min

Case Scenario Cont. BP 100/50 HR 126 ST RR 12 SPO2 100% on 100% FiO2 GCS 5 Intubated Head CT negative

To cool or not to cool Does this patient meet the criteria for induced hypothermia post cardiac arrest ?????

Why should we cool

Cardiac Arrest Abrupt loss of cardiac function Statistical Update Out of hospital cardiac arrest (OHCA) In hospital cardiac arrest (IHCA) Incidence Survival rate 2013 359,400 9.5% 209,900 23.9% 2012 382,800 11.45 23.1% Abrupt loss of cardiac function Cardiac arrest is the leading cause of death in North America 330,000 deaths per year in the US Leading cause of neurologic injury 1/3rd of survivors have irreversible cognitive dysfunction Erb, Hravnak & Rittenberger, 2012; AHA statistical Update, 2013

Cardiac Arrest Picture from http://www.firstaidforfree.com/what-is-the-chain-of-survival

Historical Perspective Fourth and fifth century BC: Hippocrates advised snow and ice packing to reduce hemorrhage 1700: Dr. Currie used cold water therapy for the treatment of several clinical disorders 1803: Covering a patient with snow hoping for the resuscitation in Russia 1812: Hypothermia (HT) was used for numbing before limb amputation in Russia 1937: Dr. Fay adopted HT as an attempt to prevent cancer cells from multiplying

History Cont. 1950: Biglow introduced moderate hypothermia (28 °C to 32 °C) during cardiac surgeries in animals to protect the brain 1958: The first reported use of TH for comatose patients after cardiac arrest by use of HT as compared to normothermia 2002: Two prospective RCT were conducted in Australia and Europe of patients with anoxic brain injury after OHCA 2002: Recommendation of TH by the International Liaison Committee on Resuscitation (ILCOR) and subsequently the American Heart Association (AHA)

TH Post Cardiac Arrest Inducing hypothermia in patients after ROSC following a cardiac arrest Initiated ASAP with a target core temperature of 32° to 34° C for 12 to 24 hours Decreases reperfusion injury Preserves cerebral function Decreases ischemic injury

AHA Guidelines Post VF/VT arrest patients who are unresponsive with a ROSC after OHCA should be cooled to 32 to 34° C (89.6-93.2 ° F) for 12 to 24 hours (Level of evidence Ib) IHCA of any initial rhythms or OHCA with an PEA/asystole (Level of Evidence IIb) Active rewarming should be avoided in comatose patients who spontaneously develops a mild hypothermia (>32 °C) during the first 48 hours after ROSC (Level of Evidence IIIc)

Inclusion Criteria for TH Witnessed arrest Post-cardiac arrest patient regardless of initial rhythm with ROSC within 60 min of initiation of ACLS Within 6 hours following cardiac arrest Maximum down time = 15 minutes Comatose state GCS ≤ 5 Intubated

Exclusion Criteria for TH Intracranial hemorrhage Major surgery within 14 days Severe systemic infection/sepsis Preexisting coagulopathies Pregnancy DNR status/terminal illness Drug induced coma MAP <60mmHg for > 30 min after ROSC Temperature < 30 °C (86F) GCS > 5

Alternative Applications of TH Traumatic brain injury Acute liver failure Aortic arch repair Cardiac bypass surgery

Clinical Trials

Clinical Data The Hypothermia after Cardiac Arrest Study Group Large randomized, controlled trial of 275 patients in nine centers in five European countries Comparison of mild hypothermia (n=137) with standard normothermia (n=138) in patients in patients who suffered cardiac arrest due to ventricular fibrillation

Clinical Data Secondary Endpoints Primary Endpoint Favorable neurologic outcome within six months after cardiac arrest Pittsburgh cerebral-performance category of 1 (good recovery); 2 (moderate disability); 3 (severe disability); 4 (vegetative state), and 5 (death) Overall mortality at six months and the incidence of complications during the first seven days Severe bleeding; pneumonia; sepsis; pancreatitis; renal failure; pulmonary edema; seizures; arrhythmias; and pressure sores

Clinical Data-Treatment All patients received standard intensive care per protocol Patients randomly assigned to the hypothermia group were cooled to a target temperature of 32°C to 34°C with the use of an external cooling device Temperature was maintained at 32°C to 34°C for 24 hours from the start of cooling Followed by passive rewarming, over a period of 8 hours

Clinical Data-Results A total of 75 of the 136 patients (55 percent) in the hypothermia group had a favorable neurologic outcome, as compared with 54 of the 137 (39 percent) in the normothermia group (risk ratio 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41% in the hypothermia group and 55% in the normothermia group (risk ratio 0.74; 95% Confidence interval, 0.58 to 0.95) The Hypothermia after Cardiac Arrest Study Group (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine, 346(8), 549-556. doi:10.1056/NEJMoa012689

Clinical Data Cochrane Database review: systematic review and meta-analysis of RCT’s to assess the effectiveness of TH in patients after cardiac arrest Main outcomes: neurologic outcome, survival, and adverse events Conclusions: Mild TH improves survival and neurologic outcomes after cardiac arrest The feasibility of TH in non-VF cardiac arrest has been confirmed, but studies have not yet shown a survival or neurological benefit Poor prognosis associated with asystole is one possible reason for this observation Arrich J, Holzer M, Havel C, Müllner M, Herkner H. (2012); Delhaye, C., Mahmoudi, M., & Waksman, R. (2011)

Pathophysiology and Mechanism of Action ICE ICE BABY Pathophysiology and Mechanism of Action

Hypothermia http://positivemed.com/2013/10/12/10-amazing-medical-procedures-20th-century

Mild Hypothermia Moderate Hypothermia Severe Confusion, impaired judgement, slurred speech Tachycardia, ↑CO Tachypnea Cold diuresis ↑Hct, ↓platelet, WBC, ↑coagulopathy Ileus, pancreatitis, gastric stress ulcers ↑ metabolic rate, hyperglycemia Increased shivering Lethargy, loss of pupillary reflex, EEG abnormalities Progressive bradycardia, ↓CO, arrhythmias, J wave on ECG Altered GI drug metabolism ↓metabolic rate, hyper-or hypoglycemia Decreased shivering Decline in EEG activity, coma, loss of ocular reflex ↓in BP and CO VF and systole Pulmonary edema, apnea ↓renal perfusion, oliguria, anuria Patient appears dead, “pseudo-rigor mortis” Kobeissi, Z., Zimmerman J. L. (2015). Hypothermia. In J.B Hall, G.A Schmidt, & J.P.Kress (Eds.), Principles of Critical Care, 4e.

Hypothermia

Mechanism of Action of TH There are several hypothesis about the neuroprotective effects of TH 1954- hypothermia could lower cerebral oxygen consumption in dogs by ~ 7% Abella, B. S., & Leary, M. ( 2015). Therapeutic hypothermia. In J. B. Hall , G. A. Schmidt, & J. P. Kress (Eds.). Principles of critical care, (4e).

Reperfusion Injury Reperfusion injury occurs after restoration of oxygen to the brain During reperfusion the immune system releases proinflammatory mediators: TNF-, interleukin-1, neutrophils, and macrophages Leads to cell death Therapeutic hypothermia can reduce the quantities and effects of these mediators Lee, R. & Asare, K. (2010). Therapeutic hypothermia for out-of-hospital arrest. American Journal of Heath-System Pharmacy, 67,

MOA This process leads to: Accumulation of oxygen free radials Activation of degradative enzymes Cellular death Therapeutic hypothermia helps to prevent this cascade of reactions by promoting cell membrane stability during oxygen deprivation Lee, R. & Asare, 2010; Scirica, B. M. (2013)

Mechanism of Action

Reperfusion Injury Reperfusion injury occurs after restoration of oxygen to the brain During reperfusion the immune system releases proinflammatory mediators: TNF-, interleukin-1, neutrophils, and macrophages Leads to cell death Therapeutic hypothermia can reduce the quantities and effects of these mediators Scirica, B. M. (2013). Therapeutic hypothermia after cardiac arrest. Circulation, 127, 24-250.

Let the cooling BEGIN….

Treatment Protocols Goal: Achieving the target temperature 32-34 degrees C as quickly as possible. Start cooling process ASAP. For every hour delay to onset of cooling, mortality increased by 20%. Can be achieved within 3-4 hrs of initiaing cooling. Effective hypothermia treatment can be less than 24 hours if initiated rapidly after ROSC. With long duration of cardiac arrest and delayed initiation of hypothermia, treatment for 48 hrs is needed to achieve good neurological outcomes. Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Treatment Protocols Preparation: Shivering, the body’s attempt at maintaining temp homeostasis, is a concern when trying to chieve a hypothermic state. Do not actively rewarm patients who are spontaneously hypothermic Treatment can be continued while in PCI laboratory and ICU Place an arterial line early for BP monitoring Continuous core temp monitor should be used: Esophageal, rectal or bladder temp Several cooling system including liquid or get heat transfer and endovascular systems incorporate a temp probe A secondary temp device should be used to monitor temp as well Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Treatment Protocols Methods: Medication Patient comfort and sedation: Narcotic nalgesia-morphine or fentanyl Sedation-midazolam or propofol Paralysis to prevent shivering: Buspirone and meperidine Train-of-four method Cold saline infusion Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Treatment Protocols External cooling with cooling blanket or suface heat ex-change device Eligibility should be confirmed, and materials should be gathered Obtain 2 cooling blankets and cables Alternatively, place heat-exchange pads on the patient Pack the patient in ice (groin, axillae, side of neck) Monitor VS and oxygen saturation Once a temp below 34 degrees C is reached, remove ice bags, and the cooling blanket or heat-exchange device Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Treatment Protocols Supportive therapy A mean arterial pressure (MAP) goal of more than 80 mmhg is preferred from a cerebral perfusion standpoint. Placing the head of the bed at 30 degrees. Monitor the patient for arrhythmia associated with hypothermia Hematolohic testing recommendation include: CBC, Chem 7, PTT, troponin, and ABG K+ values less than 3.5 mEq/L should be treated while patient is being cooled. Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Treatment Protocols Supportive therapy (cont.) Elevated serum glucose is deleterious to the injured brain. PCO2 should be maintained in the reference range (35-45 mm Hg) Skin care should be checked every 2-6 hrs for thermal injury caused by cold blankets. Regularly check the patient’s temp with a secondary temp monitoring device when cooling. Do not provide nutrition to the patient during initiation, maintenance, or rewarming phase of the therapy. Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Treatment Protocols Controlled rewarming Rewarming of the patient is begun 24 hrs after the initiation of cooling. Rewarming phase may be the most critical, as constricted peripheral vascular beds start to dilate. Peripheral hyperemia may cause hypotension. Literature recommends rewarming slowly at a temp of 0.3-0.5 degrees C every hour. Rewarming will take approximately 8 hrs. Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Cooling Methods Cooling methods include the following: Surface cooling with ice packs Suface cooling with blankets or surface heat-exchange device and ice Surface cooling helmet Internal cooling methods using catheter-based technoogies Internal cooling methods using infusion of cold fluids. Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Cooling Methods Surface cooling with ice packs This method is inexpensive and represents an appropriate way to initiate cooling. It can be messy and is less than optimal in the rate of cooling and target tem maintaenance. In addition to ice packs, evaporate cooling fans has been used.

Cooling Methods Suface cooling with blankets or surface heat-exchange device and ice Conventional surface cooling balnkets are also suboptimal because of poor surface contact with the patient’s skin. However, a combination of water-circulating cooling device and ice packs are effective at rapidly cooling patients and are fair at maintaining target temp.

Cooling Methods Surface cooling helmet The soft bonnetlike helmet contained a solution of aqueous glycerol that facilitated heat exchange.

Cooling Methods Internal cooling methods using catheter-based technoogies Two devices are currently available for use: Celsius Control System and Cool Line System. These technologies are also referred to as endovascular heat-exchange catheters. Heat exchange occurs between cooled saline that passes through the heat exchange portion of the catheter and the blood that flows over the outer surface of the catheter. Endovascular cooling and rewarming is reported to be faster and better at maintaining target temperature.

Cooling Methods Internal cooling methods using infusion of cold fluids Many have studied the effect of cold fluid infusion for the induction of mild-to-moderate hypothermia in humans. The rates of induction are variable but otherwise considered to be rapid. Cold fluid infusion with concomitant use of cooling blankets has also been shown to be efficacious. Typical infusion volume is either 30 mL/kg or 2 L of fluid using either normal saline or lactated Ringer solution.

How to (BE) Cool? Cooling Procedure Set up cooling monitors Monitor core temp: foley cath with temp probe or rectal temp probe Cooling device Internal: Alsius cooling catheter-set rate for max cooling, set target temp to 33 °C External: turn down room temp, ice packs to neck, axilla, groin, torso, 2 cooling blankets-one above and one below the patient, set to 4° C Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, 23-28. Retrieved from http://www.americannursetoday.com/therapeutic-hypothermia-after-cardiac-arrest-what-why-who-and-how/

How to (BE) Cool? Cold IV therapy Medications 30 ml/kg of cold LR or NS 0.9% over 30-60 mins ASAP post arrest Will give 2.25 C temp reduction Medications For hypotension 500 cc NS 0.9% bolus q hr 3X doses for MAP below 70 Norepinephrine drip, titrate to keep MAP above 80 Dopamine drip, for MAP below 70, titrate to keep MAP 70-80 mmHg If need to increase CO Dobutamine drip, titrate to maximum rate of 10 mcq/kg/min

How to (BE) Cool? Medications (cont) For comfort Sedation Shivering Fentanyl IVP Fentanyl drip Morphine (monitor closely BP) Sedation Versed (use with caution in renal failure patient) Propofol Drip Shivering Demerol Nimbex – start at 3 mcq/kg/min, to maintain train of foru (TOF) 2/4 Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, 23-28. Retrieved from http://www.americannursetoday.com/therapeutic-hypothermia-after-cardiac-arrest-what-why-who-and-how/

Stages of Therapeutic Hypothermia Three phases of therapeutic hypothermia Induction or initiation of cooling Refers to the rapid cooling of the patient by means of either invasive or noninvasive techniques. Maintenance Refers to the period during which the patient is kept at the target temperature of 32 to 34 degrees C. Rewarming or De-cooling Begin 18 to 24 hrs after the initiation of cooling. May be passive or actively manage. Erb, J.L., Hravnak, M., & Rittenberger, J., 2012. Therapeutic Hypothermia After Cardiac Arrest. American Journal of Nursing, 112 (7), 38-44

Induction Phase Obtained head CT Record an initial temperatures - rectal is the best Central line, peripheral IV or an intravascular cooling catheter Baseline labs: CBC and electrolytes Initiate sedation or paralytic medications Shivering- must give sedation first!!! Transfer appropriate critical care unit Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, 23-28. Retrieved from http://www.americannursetoday.com/therapeutic-hypothermia-after-cardiac-arrest-what-why-who-and-how/

Maintenance Phase During the maintenance phase, controlling the patient’s temperature within the patient’s temp the target range: 32-34 degrees C (core temp 33 degrees C) Monitor blood glucose: 100-150 mg/dl Monitor BP MAP: 65-95 mmHg This phase can last up to 18-24 hours from the time the target temp is reached (depending on facility protocol) Suppress shivering!!! Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, 23-28. Retrieved from http://www.americannursetoday.com/therapeutic-hypothermia-after-cardiac-arrest-what-why-who-and-how/

Rewarming Phase Rewarming begins 12 to 24 hours after the initiation of cooling. Rewarm slowly at a rate of 0.3-0.5 degrees C every hour Remove cooling blankets (and all ice ) One method is to set the water temperature in the cooling device to 35°C, then increase the water temperature by 0.5°C every 1-2 hours until a stable core body temperature of 36°C has been reached for 1 hour Maintain the paralytic agent and sedation until the patient’s temperature reaches 35°C Monitor the patient for hypotension secondary to vasodilation r/t rewarming D/C potassium infusion Avoid hyperthermia Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview

Potential Adverse Effects Fluid and electrolytes imbalances Arrhythmias Insulin resistance Shivering Coagulation problems Pain and sedation management Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, 23-28. Retrieved from http://www.americannursetoday.com/therapeutic-hypothermia-after-cardiac-arrest-what-why-who-and-how/

Summary

Conclusion Studies have shown that therapeutic hypothermia is an effective method for improving neurologic outcomes of patients after out-of-hospital cardiac arrest after VF The AHA/ILCOR states unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C to 34°C for 12 to 24 hours when the initial rhythm was VF. Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest Established guidelines can improve the quality of TH and effective post-resuscitation care

QUESTIONS

QUESTIONS 1. Hourly monitoring of blood glucose is recommended in the cooling phase because hypothermia leads to increased insulin resistance and decreased pancreatic activity leading to: a. Hyperglycemia b. Hypoglycemia c. Normal blood glucose level d. Unchanged glucose level 2. How does therapeutic hypothermia work in cardiac arrest? a. It reduces the brain tissue oxygen demand and slows metabolism. b. It increases intracellular acidosis and increase cerebral perfusion. c. It increases the brain tissue oxygen demand and increases metabolism.

QUESTIONS Cont. 3. What has been shown to increase the survival after cardiac arrest? Immediate recognition and activation of emergency response system, early CPR with emphasis on chest compression, rapid defibrillation, effective advanced life support, integrated post-cardiac arrest care including therapeutic hypothermia. Therapeutic hypothermia, early CPR. Early CPR with emphasis on chest compression, effective advanced life support. 4. What clinical manifestation would you not see with moderate hypothermia? Decreased shivering Loss of ocular reflex Cold diuresis Hallucinations

QUESTION Cont. 5. What is not an exclusion criterion for post-cardiac arrest therapeutic hypothermia? DNR Uncontrollable bleeding Glasgow Motor Score < 5 Significant trauma 12 hours since return of spontaneous breathing

References Abella B.S., Leary M (2015). Therapeutic Hypothermia. In Hall J.B., Schmidt G.A., Kress J.P. (Eds), Principles of Critical Care, 4e. Retrieved from http://accessmedicine.mhmedical.com.ezproxy.libraries.wright.edu/content.aspx?bookid=1340&Sectionid=80030178 Adler, J. (2014, April 30). Therapeutic Hypothermia. Medscape. Retrieved from http://emedicine.medscape.com/article/812407-overview Arrich J, Havel C, Holzer M, Herkner H. Prehospital versus in-hospital initiation of mild therapeutic hypothermia for survival and neuroprotection after out-of-hospital cardiac arrest. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD010570. DOI: 10.1002/14651858.CD010570. AHA Statistical Update, 2013. Heart Disease and Stroke Statistics-2-13 Update, A Report From the American Heart Association. Circulation, 1-240. doi: 10.1161/CIR.0B013E31828124AD Deckard, M. E., & Ebright, P. R. (2011, July). Therapeutic hypothermia after cardiac arrest: What, why, who, and how. American Nurse Today, 7, 23-28. Retrieved from http://www.americannursetoday.com/therapeutic-hypothermia-after-cardiac-arrest-what-why-who-and-how/ Delhaye, C., Mahmoudi, M. & Waksman, R. (2012). Hypothermia therapy: Neurological and cardiac benefits. Journal of the American College of Cardiology, 59(3). doi:10.1016/j.jace.2011.06.077 Erb, J.L., Hravnak, M., & Rittenberger, J., 2012. Therapeutic Hypothermia After Cardiac Arrest. American Journal of Nursing, 112 (7), 38-44 Field, J.M., Hazinski, M.F., Sayre, M.R., Chameides, L., Schexnayder, S.M., Hemphill, R., …Vanden Hoek., T.L., (2010). Part 1: Executive Summary. American Heart Association Guidelines on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 652-656, doi: 10.1161/CIRCULATIONAHA.110.970889

References Gardner,G., & MacDonald, S., 2013. Caring for Patients Receiving Therapeutic Hypothermia Post Cardiac Arrest in the Intensive Care Unit. Canadian Journal Of Cardiovascular Nursing, 23(3), 15-17 Field, J.M., Hazinski, M.F., Sayre, M.R., Chameides, L., Schexnayder, S.M., Hemphill, R., …Vanden Hoek., T.L., (2010). Part 1: Executive Summary. American Heart Association Guidelines on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation, 652-656, doi: 10.1161/CIRCULATIONAHA.110.970889 Karnatovskaia, L.V., Wartenberg, K. E., & Freeman, W. D., (2014). Therapeutic Hypothermia for Neuroprotection. Neurohospitalist, 4(3), 153-163. doi: 10.1177/1941874413519802 Kobeissi, Z., Zimmerman J. L. (2015). Hypothermia. In J.B Hall, G.A Schmidt, & J.P.Kress (Eds.), Principles of Critical Care, 4e. Retrieved from http://accessmedicine.mhmedical.com.ezproxy.libraries.wright.edu/content.aspx?bookid=1340&Sectionid=80030178. Lee, R. & Asare, K. (2010). Therapeutic hypothermia for out-of-hospital arrest. American Journal of Heath-System Pharmacy, 67, 1229-1237. doi: 10.2146/ajhp090626 Scirica, B.M. (2015). Therapeutic Hypothermia After Cardiac Arrest. Circulation, 244-250. doi: 10.1161/CIRCULATIONAHA.111.076851 The Hypothermia after Cardiac Arrest Study Group (2002). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine, 346 (8), 549-556. doi:10.1056/NEJMoa012689