Focus On: Therapeutic Hypothermia After Cardiac Arrest
By SACHIN PATEL, M.D., and ALAN KUMAR, M.D.
Dr. Patel is Director of Quality in the Department of Emergency Medicine at Community Hospital in Muster, Ind. Dr. Kumar is Chairman and Medical Director of the Department of Emergency Medicine at Community Hospital in Munster, Ind., and a Clinical Instructor at the University of Chicago Medical School. Medical Editor Dr. Robert C. Solomon is an attending emergency physician at Southwest Regional Medical Center in Waynesburg, Pa., and clinical assistant professor of emergency medicine at the West Virginia School of Osteopathic Medicine, Lewisburg. Nancy Calaway is an ACEP staff member who reviews and manages the ACEP Focus On series.
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. Patel, Dr. Kumar, Dr. Solomon and Ms. Calaway 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: Therapeutic Hypothermia After Cardiac Arrest" is approved by the American College of Emergency Physicians for one ACEP Category I credit.
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.
Questionnaire Is Available Online
This educational activity is designed for emergency physicians and should take approximately 1 hour to complete. Participants will need an Internet connection through Firefox, Safari or Internet Explorer 6.0 or above to complete this Web-based activity. The CME test and the evaluation form are located online at www.ACEP.org/focuson.
The participant should, in order, review the learning objectives, read the article, and complete the CME post-test/evaluation form to receive up to 1 ACEP Category I credit and 1 AMA PRA Category 1 CreditTM. You must score at least 70 percent to receive credit. You will be able to print your CME certificate immediately.
This article was published online May 1, 2011. The credit for this CME activity expires April 30, 2014.
After reading this Web-based article, the physician should be able to:
- Recognize and treat uncommon presentations of common pathology and common presentations of rare pathology so that physicians have exposure to these rare conditions.
- List the exclusion criteria for patients who might qualify for therapeutic hypothermia.
- Recognize the potential complications for patients who have been cooled.
- Describe the various devices used in therapeutic cooling and thier advantages and disadvantages.
Each year in the United States, it is estimated that between 350,000 and 450,000 patients suffer witnessed out-of-hospital sudden cardiac arrest (OHSCA). Around 100,000 of these are subjected to resuscitation efforts and 40,000 of these survive to hospital discharge.1 The incidence of OHSCA is estimated to be between 0.04% and 0.19%, and among patients in whom resuscitation is attempted, between 14% and 40% achieve return of spontaneous circulation (ROSC) and are admitted to the hospital.2 Of these, just 7%-30% have good neurologic outcomes at hospital discharge.3 Concerted efforts targeting the resuscitated population may be able to improve these numbers.
In 2010, the Emergency Cardiac Care Committee of the American Heart Association (AHA) declared that doubling survival from cardiac arrest would be one of its "Impact Goals." In the past, much effort has been focused on the initial objectives of post-cardiac arrest care, including optimizing cardiopulmonary function, triaging patients prehospital to critical care centers equipped for appropriate post-cardiac arrest care, and prevention of recurrent arrest by addressing precipitating factors. However, recent efforts have broadened to focus on secondary objectives of post-cardiac arrest care, such as rehabilitation care and optimizing mechanical ventilation to prevent lung injury.4
The focus of this article is on the essentials of one of these secondary objectives: therapeutic hypothermia in the post-cardiac arrest setting to optimize survival and neurologic outcomes.
Therapeutic hypothermia is a relatively new concept for preservation of neurologic function in comatose patients
after cardiac resuscitation. It entails cooling the patient's core body temperature in a controlled way to maintain a range of 32-34°C for 24 hours in a critical care setting once the patient has been stabilized from resuscitation. Ideally, the cooling should begin within a few hours of arrest, though there is some lack of consensus on the ideal onset timeframe.4
After cardiorespiratory arrest, resuscitation reestablishes blood flow to a starved brain. Overall, it is clearly a good idea to restore the brain's energy stores and function, but reperfusion can trigger some harmful chemical cascades. Reperfusion has been implicated in the generation of free radicals and other harmful chemical mediators that lead to "postresuscitation syndrome" and multifocal brain damage via neuronal apoptosis.5 During hypothermia, the ability to survive anoxic low-flow states is dramatically increased.6 Furthermore, it is postulated that therapeutic hypothermia can reduce processes that lead to tissue damage such as biosynthesis and the release and uptake of several catecholamines and neurotransmitters. Other beneficial effects include preserving the blood-brain barrier, protecting existing energy stores, restoring cerebral microcirculation, and potentially decreasing intracranial pressure.2
Though physicians as early as Hippocrates recognized the benefits of therapeutic hypothermia in attenuating injury, only more recently has the evidence in favor of its use in cardiac arrest begun to warrant its use.7 Several authorities have endorsed the use of therapeutic hypothermia in eligible patients (see next section), including the International Liaison Committee on Resuscitation, the AHA, and the European Resuscitation Council.
Formal studies as early as the 1950s began to demonstrate the benefits of hypothermia after cardiac arrest. For instance, a study by Benson et al. in 1959 of 19 patients showed that 6 of 12 patients who were cooled to a target of 31-32°C survived after cardiac arrest, compared with only 1 of 7 in the uncooled group.8
More recently, two landmark randomized, controlled trials - one done in Australia and one in Europe - were published in the New England Journal of Medicine in 2002 showing that therapeutic hypothermia has neuroprotective effects after resuscitation from cardiac arrest. In the Australian trial by Bernard et al., 77 comatose survivors of cardiac arrest were randomized to hypothermia (treatment) vs. normothermia (control) groups. They found that 49% of the 43 patients treated with therapeutic hypothermia survived with favorable neurologic outcomes, compared with just 26% of the 34 normothermia group (P = .05).9
In the European multicenter trial by the Hypothermia After Cardiac Arrest Study Group, 275 comatose survivors were randomized to treatment (N = 136) and control (N = 137) groups. In the hypothermia group, 55% had a favorable neurologic outcome 6 months later, compared with 39% in the control group (P = .009). Therapeutic hypothermia significantly improved functional recovery at hospital discharge (55% vs. 39%, number needed to treat [NNT] = 6) and improved 6-month mortality rate, compared with the control, noncooled group (41% vs. 55%, NNT = 7).10
The numbers needed to treat before seeing a benefit from therapeutic hypothermia are remarkably low, approaching those seen with other important therapeutic interventions, such as percutaneous coronary intervention.
More data are emerging for the use of therapeutic hypothermia in post-cardiac arrest patients and numerous other conditions, including traumatic brain injury, hemorrhagic shock, and even neonatal hypoxic encephalopathy. Currently, at least 19 clinical trials are ongoing to further investigate the benefits of therapeutic hypothermia on ROSC and other conditions.
Who Is Eligible?
To be eligible for therapeutic hypothermia, patients must meet all of the following criteria:
- Be an adult successfully resuscitated from witnessed arrest from presumed cardiac cause.
- Be comatose and intubated.
- Have an initial rhythm of ventricular fibrillation or nonperfusing ventricular tachycardia.
- Be hemodynamically stable after resuscitation (though some data support using therapeutic hypothermia in patients in cardiogenic shock after resuscitation).
Who Is Not Eligible?
Do not start therapeutic hypothermia on any patients who meet any of the following exclusion criteria:
- Tympanic membrane temperature less than 30°C on admission.
- Terminal illness.
- Comatose prior to cardiac arrest.
- Inherited blood coagulation disorders.
How Do You Cool?
- Do not delay percutaneous coronary intervention if it is indicated. Cooling can be started and continued in the cath lab.
- Insert a core temperature monitor, which can be either a specially equipped Foley catheter, a specially equipped central line (Swan-Ganz catheter or other specific devices), or an esophageal probe.
- Infuse 20-30 cc/kg of cold (4°C) lactated Ringer's (LR) or normal saline (NS) over 30 minutes to initiate cooling (unless patient is on dialysis or has pulmonary edema).
- Employ your hospital's cooling system (see options in next section) to reach a target temperature of 32-34°C.
- Maintain that temperature range for 24 hours. Use sedation as needed and paralytics if patient is shivering.
- Monitor labs every 4 hours: basic metabolic profile (BMP), prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR), complete blood count (CBC), troponin, arterial blood gases (ABG). Note that elevations of amylase/lipase of unclear significance have been reported.
- Nursing maintenance care includes lacrilubing the eyes, monitoring urine output, monitoring vital signs, and maintaining tight glycemic control.
- During the rewarming phase, raise the patient's core temperature by 0.3-0.5°C per hour up to 36.5°C.
- Don't provide supplemental nutritional support during the initiation, maintenance, or rewarming phases.
Options for Cooling
Two main methods are available to induce therapeutic hypothermia in a variety of clinical settings: surface cooling and core cooling. The specific choice of tools is dependent on the needs of your institution (for example, is cost more important than ease of use, or vice versa?), but the classes of tools are reviewed in this article.
Surface cooling is typically the fastest way to begin cooling, though it can be the most difficult to regulate. The most basic way to cool a patient is to use numerous ice packs applied to the head, neck, torso, and limbs. This method is cheap, uses materials quickly available in most emergency departments, and is intuitive to most staff. However, accurate temperature regulation can be difficult when using ice packs alone. Several commercially available tools, such as cooling blankets and gel pads, can be used to achieve surface cooling.
Cooling blankets will typically cover much of the patient's body; water circulates through the blanket for conductive temperature regulation. The major advantages of cooling blanket systems are their low cost and quickness of application. One drawback of these systems is they reduce access to the patient for nursing care and for procedures like cardiopulmonary resuscitation and defibrillation. Further, there is a risk of thermal injury from inadvertent punctures of the blanket.
Gel pad systems cover less of the body and provide easier access to the patient for procedures and nursing care. Gel pads can be more effective than blankets in achieving and maintaining temperatures in the desired range because they are applied directly to the body. However, gel pads can be more time consuming to apply than blankets, especially on obese patients. Some gel pad systems reduce the risk of thermal injury from pad punctures by using negative pressure to pull water through the pads. Initial and recurrent costs tend to be much higher for gel pad systems than for blankets.
Surface cooling systems in general have the advantage of being noninvasive and quickly applicable to the patient. They have the disadvantage of requiring a separate mechanism of core-temperature monitoring, such as a Foley or nasogastric tube equipped with a thermometer or repeated rectal temperatures. In addition, speed of cooling and ability to maintain temperature within the desired range can vary widely for the different systems.
Core cooling techniques employ more invasive methods to reach and maintain hypothermia. Thermometer-equipped nasogastric tubes can be used to infuse cooled oral fluids and monitor esophageal temperature, though the risk of aspiration makes this less desirable. Cooled intravenous fluids can be infused by peripheral lines or standard central lines, though a separate temperature monitoring mechanism is needed.
Some commercially available intravenous cooling catheters (either made of metal or containing balloons filled with cold saline) also have built-in thermometers for temperature monitoring. The advantage of these systems is that because nearly all patients requiring cooling also will require a central line and invasive temperature monitoring, these needs can be met with a single catheter, and there is no external barrier impeding physical access to the patient for other procedures. The main drawbacks of intravenous cooling catheter systems are high cost and invasiveness.
Although the use of therapeutic hypothermia is strongly supported by the existing literature, clinicians must be careful to use it in the correct patient population and be aware of potential problems arising from its use. Cooling has the effect of immune suppression, making it a relative contraindication in patients with suspected sepsis. Overcooling also will lead to more potential complications from induced coagulopathies. Even in the target temperature range, complications from ROSC and hypothermia are numerous and include shivering, fever, hypotension, hyperglycemia, electrolyte abnormalities (especially potassium), bradycardia, and continued cardiac ischemia. Failure to monitor for and address these adjunctive conditions can lead to morbidity and mortality despite appropriate initiation of therapeutic hypothermia.
Creating a successful therapeutic hypothermia protocol at your hospital is a complex undertaking requiring concerted efforts by many constituents. Emergency physicians and nurses, critical care nurses, cardiologists, neurologists, intensivists, and hospital administrators should be involved in the decisions about what equipment to purchase and in the development of your hospital's specific protocol.
Head-to-head comparisons of the commonly used systems for cooling a patient have not showed a definitive advantage of any particular device. The start-up costs range from the cost of ice packs to expensive comprehensive commercial devices, which cost anywhere between $5,000 and $50,000, plus the cost of disposable accessories per patient use. Choose the device that would best serve your hospital's cardiac, neurologic, and emergency patients at the price point and convenience point that fits your needs. Remember that therapeutic cooling is a resource-intensive intervention, and some hospitals may elect to transfer eligible patients to centers providing higher levels of care.
Patients who have witnessed sudden cardiac arrest and are comatose after return of spontaneous circulation can benefit from therapeutic hypothermia. Initial studies of therapeutic hypothermia are promising, and future developments will improve our understanding of the best methods of cooling.
Significant hurdles to implementing a program include intensive use of resources, institutional commitment from multiple specialties for continued patient care, potential complications during cooling such as coagulopathy and hypotension, and the cost of the various devices. Multiple studies showing impressive results in favorable neurologic outcomes for the proper patients make the difficult task of developing a program worthwhile.