From the EM Model
3.0 Cardiovascular Disorders
3.1 Cardiopulmonary Arrest

An estimated 155,000 cases of EMS-treated sudden cardiac arrest occur each year in the United States.¹ Despite advances in cardiopulmonary resuscitation (CPR) and periodic changes in guidelines, most of these victims do not survive to hospital admission or die of multisystem organ failure within a few days. Among those who survive there is a high incidence of brain damage.^2,3 It has long been noted that patients with cardiac arrest who suffer cold-water drowning or arrest in the cold seem to do better than patients who arrest in a warm environment, and hypothermia has long been used in cardiothoracic surgery. These observations led researchers to investigate intentionally cooling resuscitated victims of cardiac arrest. In Bernard’s two early studies from Australia, mortality rates dropped from 77% to 45% and from 68% to 51%, while good neurologic outcome rose from 14% to 50% and 26% to 49% when cardiac arrest victims were cooled.^4,5 Similar results were seen in the European Hypothermia After Cardiac Arrest (HACA) trial, where 6-month mortality rates dropped from 55% to 41% and good neurologic outcome rose from 39% to 55%.⁶ Since then, additional studies have shown improved survival, although some are small, nonrandomized, with historical controls, and a few demonstrate trends rather than statistically significant differences.^4-20 In the setting of percutaneous coronary intervention (PCI) following a cardiac arrest, cooling also increased survival with good neurologic outcome from 16% to 55% (p=0.001).⁸

Case Presentation

A 55-year-old man collapses in his office. Coworkers call EMS and are instructed in bystander CPR. Paramedics find the patient in ventricular fibrillation and promptly defibrillate. After 2 more minutes of CPR, the patient is defibrillated a second time and shortly regains a palpable radial pulse. The monitor shows sinus rhythm with a rate of 70; blood pressure is 100/70. He is unresponsive to sternal rub and has no gag reflex, so he is intubated. A 12-lead ECG showing an anterolateral ST-segment elevation myocardial infarction (STEMI) is transmitted to the hospital. The emergency physician activates the cardiac catheterization laboratory. As they begin the 20-minute transport to the emergency department, the paramedics ask about hypothermia.

Pathophysiology

It is thought that cooling the body to between 32°C and 34°C (89.6°F and 93.2°F) decreases brain oxygen use and limits brain damage after cardiac arrest.²¹ Cerebral reperfusion injury is caused by a multitude of factors, including free radical production, intracellular calcium influx, pathologic protease cascade, mitochondrial damage, and apoptosis by activation of cell-death signaling pathways.^7,21,22 These reactions begin within the first few hours following a cardiac arrest and continue for several days, providing a window for neuroprotective strategies such as therapeutic hypothermia.²² The cerebral metabolic rate decreases by 6% to 7% for each 1°C (1.8°F) decrease in temperature.²¹ Decreasing metabolic rate and oxygen consumption after the arrest decreases destructive enzymatic reactions and free radical production.^6,21

Cooling the body presumably also reduces overall metabolic workload and demand on the heart. There seems to be a direct cardioprotective effect as well. Following reperfusion, the acidic pH caused by tissue ischemia is rapidly corrected, and the Na+/Ca++ pump is activated, causing a rapid influx of calcium into the cells, which causes irreversible cell damage and myocardial stunning.²³ One animal study found that hypothermia reduced myocardial injury by preventing intracellular Ca++ overload at reperfusion via inhibition of the Na+/Ca++ exchanger.²³ Another animal study found hypothermia significantly improved immediate myocardial salvage and long-term left ventricular remodeling after infarct reperfusion.²⁴

CRITICAL DECISION

Who should get therapeutic hypothermia?

Traditionally, cooling has been restricted to victims of ventricular fibrillation cardiac arrest, and this was reflected in both the 2005 and 2010 guidelines from the European Resuscitation Council (ERC) and the American Heart Association (AHA). Increasingly, however, cooling is being successfully applied to other rhythms. Bernard reports a 7% to 17% favorable outcome at hospital discharge for asystole or pulseless electrical activity (PEA) depending on when and where the cooling took place, while Testori reports an odds ratio of 1.84 for good neurologic outcome when these patients were cooled.^25,26 This appears to be especially true when the time interval from collapse to return of spontaneous circulation is brief.²⁷

Given that the prognosis is so poor after cardiac arrest, it is reasonable to attempt hypothermia on all adult patients with cardiac arrest, regardless of presenting rhythm.

CRITICAL DECISION

When should induction of therapeutic hypothermia begin?

The current recommendation for cooling is that it begin after return of spontaneous circulation, but the ideal timing of induction has not yet been clearly established. Results of some animal studies have suggested that the earlier therapeutic hypothermia is instituted the better, and that delayed hypothermia might have no benefit, a finding that is supported in at least one recent clinical trial.^25,28,29

CRITICAL DECISION

What methods can be used to induce therapeutic hypothermia?

The best method of therapeutic hypothermia has not been determined, and none is endorsed by the AHA or the ERC.^2,30 Ice-cold intravenous infusions, ice packs, cooling blankets, noninvasive surface cooling devices, and endovascular cooling have all been used.^{2,8-11,17-19,30,31} The location of cooling and the expense or complexity of the equipment ultimately will dictate what method is used. If cooling is initiated in the field, ice packs and cold saline are the simplest and least expensive. In a monitored environment, endovascular cooling at a rate of 1.1°C (2°F) per hour provides more precise control and may prevent the overshoot sometimes seen with surface cooling, but whether this affects outcome is unknown.^30,32,33

CRITICAL DECISION

How should therapeutic hypothermia be maintained?

Temperature should be closely monitored to keep the patient in the 32° C to 34° C (89.6° F to 93.2° F) range.² The patient should be paralyzed and sedated to prevent shivering, which increases the metabolic rate and oxygen demand and may increase the incidence of myocardial infarction.²¹ However, reduction of core temperature by 1°C typically takes about 30 minutes using cold saline and does not trigger a thermoregulatory response, allowing paralytics to be delayed until the patient’s arrival in the emergency department, even if cooling is begun in the ambulance.¹⁹ As these are comatose patients who are going to be pharmacologically paralyzed, a secure airway should be in place prior to inducing hypothermia. Cooling should be continued for 12 to 24 hours, after which patients should be rewarmed slowly (0.25°C to 0.5°C per hour), and subsequent hyperthermia should be avoided.^2,7,22

CRITICAL DECISION
What are the complications of therapeutic hypothermia?
In the ERC HACA study, 3% of patients suffered hemorrhage and 6% suffered arrhythmia, but overall there were no deaths attributed to therapeutic hypothermia, and there was no significant difference in complication rates between patients cooled by the endovascular method and those cooled by other methods.33 The initial randomized controlled trial by Bernard found no clinically significant cardiac arrhythmias but did find clinically unimportant hyperkalemia.⁵ They also noted an increase in hyperglycemia in the hypothermia group.5 It is reasonable to monitor for cardiac arrhythmia, hemorrhage, hyperglycemia, hyperkalemia, and infection.^2,7

CRITICAL DECISION

Can a patient undergoing therapeutic hypothermia receive cardiac catheterization?

A feasibility study of 40 patients who underwent PCI and therapeutic hypothermia compared to historic controls with PCI only found no difference in peak lactate, need for vasopressors or inotropes, aortic balloon pump use, repeat cardioversion/defibrillation, renal function, oxygen requirements during mechanical ventilation, or use of antiarrhythmics, while demonstrating a 39% increase in neurologically intact survival.⁸ A 2012 study published in Resuscitation reported similar findings.³⁴ It is therefore reasonable to start cooling prior to PCI and to continue it throughout the procedure as long as the cooling method does not interfere with performance of the procedure.

Case Resolution

En route to the hospital with the man who had arrested at work, paramedics started therapeutic hypothermia using icepacks in the patient’s axillae and groin and administering a 30-mL/kg bolus of normal saline cooled to 4° C (39.2° F). Ventilation was provided by bag-valve-mask, carefully avoiding hyperventilation. On arrival at the emergency department, the patient’s vital signs were blood pressure 110/70, heart rate 80, and temperature 95.9° F (35.5° C). An esophageal temperature probe was placed, ice packs were changed, and the patient was placed on a cooling blanket before being transported to the cardiac catheterization laboratory. Following balloon angioplasty and stenting, the patient went to the ICU, where hypothermia was continued for 24 hours. He was then slowly rewarmed at 0.25° C (0.5° F) per hour while being weaned off the sedation, paralytics, and ventilator. Finally, after 10 days and placement of an internal defibrillator, he was discharged home with a full neurologic recovery.

Summary

Historically, rates of survival with full neurologic recovery after cardiac arrest have been dismal. Therapeutic hypothermia appears to increase a patient’s chance of survival with a good neurologic outcome. Patients with a witnessed ventricular fibrillation arrest, bystander CPR, and return of spontaneous circulation prior to transport to the emergency department already have the best chance of survival, and therapeutic hypothermia further improves their chances for a good neurologic recovery. Other rhythms may benefit too. Despite the evidence and AHA guidelines, institutions have been slow to adopt therapeutic hypothermia policies. Studies showed that only 23% to 26% of US physician members of the Society for Academic Emergency Medicine, the AHA, and the American Thoracic Society and only 16% of US emergency physicians use therapeutic hypothermia.^35,36 Therapeutic hypothermia has the potential to save lives, and we advocate more widespread use.

References

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2. ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2005 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005;112(S24):IV1-IV203.
3. Majersik JJ, Silbergleit R, Meurer WJ, et al. Public health impact of full implementation of therapeutic hypothermia after cardiac arrest. Resuscitation. 2008;77:189-194.
4. Bernard SA, Jones BM, Horne MK. Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med. 1997;30(2):146-153.
5. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-563.
6. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346(8):549-556.
7. Wolfrum S, Pierau C, Radke P, et al. Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention. Crit Care Med. 2008;36(6):1780-1786.
8. Knafelj R, Radsel P, Ploj T, Noc M. Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation. 2007;74(2):227-234.
9. Schefold JC, Storm C, Joerres A, Hasper D. Mild therapeutic hypothermia after cardiac arrest and the risk of bleeding in patients with acute myocardial infarction. Int J Cardiol. 2009;132(3):387–391.
10. Tiainen M, Poutiainen E, Kovala T, et al. Cognitive and neurophysiological outcome of cardiac arrest survivors treated with therapeutic hypothermia. Stroke. 2007;38(8):2303-2308.
11. Bro-Jeppesena J, Kjaergaarda J, Horstedb T, et al. The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest. Resuscitation. 2009;80(2):171–176.
12. Oddo M, Schaller MD, Feihl V, et al. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med. 2006;34(7):1865-1873.
13. Laish-Farkash A, Matetzky S, Kassem S, et al. Therapeutic hypothermia for comatose survivors after cardiac arrest. Isr Med Assoc J. 2007;9(4):252-256.
14. Holzer M, Mullner M, Sterz F, et al. Efficacy and safety of endovascular cooling after cardiac arrest: cohort study and Bayesian approach. Stroke. 2006;37(7):1792-1797.
15. Gaieski D, Band R, Abella B, et al. Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation. 2009;80(4):418–424.
16. Oddo M, Ribordy V, Feihl F, et al. Early predictors of outcome in comatose survivors of ventricular fibrillation and non-ventricular fibrillation cardiac arrest treated with hypothermia: a prospective study. Crit Care Med. 2008;36(8):2296-2301.
17. Kim F, Olsufka M, Longstreth WT, et al. Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with rapid infusion of 4 degrees C normal saline. Circulation. 2007;115:3064-3070.
18. Bruel C, Parienti JJ, Marie W, et al. Mild hypothermia during advanced life support: a preliminary study in out-of-hospital cardiac arrest. Crit Care. 2008;12(1):R31.
19. Belliard G, Catez E, Charron C, et al. Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation. Resuscitation. 2007;75(2):252-259.
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23. Inoue K, Ando S, Gyuan F, et al. A study of the myocardial protective effect of rapid cooling based on intracellular Ca, intracellular pH, and HSP70. Ann Thorac Cardiovasc Surg. 2003;9(5):301-306.
24. Hamamoto H, Sakamoto H, Leshnower BG, et al. Very mild hypothermia during ischemia and reperfusion improves postinfarction ventricular remodeling. Ann Thorac Surg. 2009;87(1):172-177.
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26. Testori C, Stertz F, Behringer W, et al. Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation. 2011;82(9):1162-1167.
27. Soga T, Nagao K, Sawano H, et al. Neurological benefit of therapeutic hypothermia following return of spontaneous circulation for out-of-hospital non-shockable cardiac arrest. Circ J. 2012;76:2579-2585.
28. Kuboyama K, Safar P, Radovsky A, et al. Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia in cardiac arrest in dogs: a prospective randomized study. Crit Care Med. 1993;21:1348-1358.
29. Nozari A, Safar P, Stezoski SW, et al. Critical time window for intra-arrest cooling with cold saline flush in a dog model of cardiopulmonary resuscitation. Circulation. 2006;113:2690-2696.
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31. Kamarainen A, Virkkunen I, Tenhunen J, et al. Induction of therapeutic hypothermia during prehospital CPR using ice-cold intravenous fluid. Resuscitation. 2008;79(2):205-211.
32. Flint AC, Hemphill JC, Bonovich DC. Therapeutic hypothermia after cardiac arrest: performance characteristics and safety of surface cooling with or without endovascular cooling. Neurocrit Care. 2007;7:109-118.
33. Arrich J, The European Resuscitation Council Hypothermia After Cardiac Arrest Study Group. Clinical application of mild therapeutic hypothermia after cardiac arrest. Crit Care Med. 2007;35(4):1041-1047.
34. Maze R, Le May MR, Hibbert B, et al. The impact of therapeutic hypothermia as adjunctive therapy in a regional primary PCI program. Resuscitation. 2012 Aug 21. pii S0300-9572(12)00398-X. doi:10.1016/j.resuscitation.2012.08.002. [Epub ahead of print].
35. Abella BS, Rhee JW, Huang KN, et al. Induced hypothermia is underused after resuscitation from cardiac arrest: a current practice survey. Resuscitation. 2005;64:181-186.
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Contributor Disclosures

Contributors: Dr. Bhalla is an associate professor of emergency medicine at Northeast Ohio Medical University (NEOMED) and Emergency Medicine

Resident Research Director, Summa Akron City Hospital in Akron, Ohio. Dr. Mencl is a professor of emergency medicine at NEOMED and director of the Summa Center for EMS, in

Akron. Dr. Robert C. Solomon is Medical Editor in Chief of ACEP News and editor of the Focus On… Critical Decisions series, core faculty in the emergency

medicine residency at Allegheny General Hospital, Pittsburgh, Pennsylvania, and assistant professor in the Department of Emergency Medicine at Temple University School of Medicine,

Philadelphia. Mary Anne Mitchell is an ACEP staff member who reviews and manages the ACEP Focus On… Critical Decisions

series.

Disclosures: In accordance with the Accreditation Council for Continuing Medical Education (ACCME) Standards and American College of Emergency Physicians policy, all individuals in control of content must disclose to the program audience the existence of significant financial interests in or relationships with manufacturers of commercial products that might have a direct interest in the subject matter.

Dr. Bhalla, Dr. Mencl, Dr. Solomon, and Ms. Mitchell have disclosed that they have no significant relationships with or financial interests in any commercial companies that pertain to this article. There is no commercial support for this activity.

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). The American College of Emergency Physicians is accredited by the ACCME to provide continuing medical education for physicians.

The American College of Emergency Physicians designates this enduring material for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

“Focus On…Critical Decisions: Therapeutic Hypothermia After Cardiac Arrest” is approved by the American College of Emergency Physicians for 1 ACEP Category I credit.

Disclaimer: ACEP makes every effort to ensure that contributors to College-sponsored programs are knowledgeable authorities in their fields. Participants are nevertheless advised that the statements and opinions expressed in this article are provided as guidelines and should not be construed as College policy. The material contained herein is not intended to establish policy, procedure, or a standard of care. The views expressed in this article are those of the contributors and not necessarily the opinion or recommendation of ACEP. The College disclaims any liability or responsibility for the consequences of any actions taken in reliance on those statements or opinions.