Current Evidence In Therapeutic Hypothermia For Postcardiac Arrest Care

Current Evidence In Therapeutic Hypothermia For Postcardiac Arrest Care

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Table of Contents
Table of Contents
  1. Abstract
  2. Case Presentations
  3. Definition: Moderate Hypothermia
  4. Critical Appraisal Of The Literature
  5. Etiology And Pathophysiology: Postcardiac Arrest Syndrome
    1. Postcardiac Arrest Brain Injury
    2. Postcardiac Arrest Myocardial Injury
    3. Systemic Ischemic Reperfusion Response
  6. Differential Diagnosis: Disease Management Considerations
  7. Prehospital Care
  8. Emergency Department Evaluation
  9. Diagnostic Studies
  10. Treatment
    1. Cooling Systems
      1. External Cooling Systems
      2. Internal Cooling Systems
    2. Cooling System Summary
    3. Induction
    4. Maintenance Phase
  11. Critical Care Basics
    1. Shivering Response
  12. Controversies
  13. Disposition
    1. Rewarming
  14. Summary
  15. Risk Management Pitfalls For Therapeutic Hypothermia
  16. Cost-Effective Strategies For Therapeutic Hypothermia
  17. Case Conclusion
  18. Clinical Pathway For The Application Of Therapeutic Hypothermia
  19. Tables and Figures
    1. Table 1. Published Guidelines Specific To Therapeutic Hypothermia
    2. Table 2. Inclusion Criteria For Induced Hypothermia Must Have All
    3. Table 3. Exclusion Criteria For Induced Hypothermia
    4. Table 4. Common Laboratory Changes Associated With Induced Hypothermia
    5. Table 5. Common Cardiac Changes
    6. Table 6. Procedures Recommended For Hemodynamic Monitoring
  20. Induced Hypothermia Protocol Example
  21. References


Cardiac arrest is one of the most intense clinical scenarios faced by the emergency clinician. The challenges are twofold: restarting spontaneous circulation and simultaneously attempting to find―and then reverse―the cause of the cardiac arrest. Chaos, confusion, fear, misinformation, and missing information are all common obstacles to managing the patient in cardiac arrest. To assist emergency clinicians in this situation, protocols such as Basic Life Support and Advanced Cardiovascular Life Support (ACLS) have been codified and refined in the past decade.1-3 These protocols have helped clinicians to think in a clear and goal-oriented manner and lead to one of two clinical outcomes: If their efforts are unsuccessful, the patient will be pronounced dead. If their efforts are successful, however, they will oftentimes find themselves facing the question (though perhaps not openly admitting it) of, “Now what?”

With the return of spontaneous circulation (ROSC), one of the emergency clinician’s initial challenges has been met. The heart is spontaneously circulating blood. The second challenge of attempting to find and reverse the cause of the cardiac arrest remains, however; efforts now shift to these investigative ends while the emergency clinician simultaneously attempts to keep the newly resuscitated patient stable. Within the last several years, a more specific continuing treatment plan―beyond that of simple stability―has emerged. This plan is aimed at addressing the patient’s postarrest pathology, which includes the initial disease process that led to the cardiac arrest and the aftermath of the event.4

No organ system is exempt from the insult of cardiac arrest. Cardiac, neurologic, renal, and hepatic functions all suffer, not only from the momentary decrease in perfusion, but also from the massive inflammatory responses/cascades present during reperfusion.5 Historically, hypothermia has appeared to confer some degree of protection from these insults.6 Case reports of victims of cold water drowning who make full neurologic recoveries after having been in arrest for extended periods are well-known.7-10 Brain death—or severe neurologic compromise—is an unfortunate and devastating result of cardiac arrest. This event undermines all prior efforts to save the patient. Although other organ systems can be compensated for, artificially circumscribed, or even replaced (as is the case with renal and liver failure after cardiac arrest), neurologic function must stand on its own. It can determine the extent to which the patient is functional, even despite a perfusing rhythm.

Simple speculation about the practice of inducing hypothermia after cardiac arrest, followed by intense and promising research, has led to its use for the specific purpose of improving neurologic outcomes.11 A growing body of evidence12 suggests that control of body temperature (ie, preventing hyperthermia and, more specifically, inducing hypothermia) should become the standard of care. Many emergency medical services (EMS) providers are also investigating the use of specific guidelines and procedural protocols for inducing hypothermia in postcardiac arrest patients.13 A wide variation still exists in the technical application of hypothermia therapy, however.

Case Presentations

The ring of the red notification phone breaks the relative calm of an otherwise typical Monday morning and heralds the arrival of a critically ill patient. The dispatcher announces that EMS is on the way with a 57-year-old man in cardiac arrest, with an ETA of 3 minutes. Shortly after preparations for their arrival are complete, EMS personnel enter with CPR in progress and the patient already intubated. As monitor/defibrillator attachment, ETT placement confirmation, additional IV access, and complete exposure of the patient occur, you hear more about the clinical scenario from EMS. Mr. I.C. is a 57-year-old male who was moving furniture when, as described by witnesses, he complained of difficulty catching his breath and a slight tightness in his chest. He began coughing violently, vomited once, gasped, and collapsed. Emergency medical services personnel state that they arrived approximately 20 minutes after the patient had collapsed, with CPR in progress. The patient was intubated in the field, and EMS reports that the initial rhythm was PEA. Upon the patient’s arrival in the ED, the rhythm is noted to be ventricular fibrillation. Defibrillation is attempted twice over the next 4 minutes, with concomitant administration of medications. During the next rhythm check, QRS complexes are noted on the monitor and a pulse is palpated. The patient has had a return of spontaneous circulation, apparently 50 minutes from onset of the arrest. As you initiate postresuscitation care, you consider the patient’s prognosis and wonder if he qualifies for therapeutic hypothermia; ie, will therapeutic hypothermia make a difference in his outcome?

Definition: Moderate Hypothermia

Early research suggested that at temperatures greater than 30°C (86°F), the benefits of hypothermia outweigh the risks of adverse effects, whereas temperatures less than 30°C (86°F) are associated with a greater incidence of more severe adverse effects.14 The goal temperature for hypothermia used most often in studies showing improvement of outcomes was 32°C (90°F) to 33.9°C (93°F).11,15 The literature has recently proposed that this range be referred to as moderate therapeutic hypothermia.16 The goal of this literature review is to assist the emergency clinician in adapting the known body of evidence and techniques into an easily applicable protocol to maximize outcomes after cardiac arrest. The online version of this issue includes the Mount Sinai Hospital Induced Hypothermia Protocol and Post- ROSC Care Package documents (available at, which readers may find helpful in establishing institutional protocols.

Critical Appraisal Of The Literature

The MEDLINE® database was searched for articles published from 1950 to October 2010 that used the term hypothermia. This generalized search yielded well over 3000 publications. The effort was narrowed to English publications using 1 or more of the following terms: induced, therapeutic, cardiac arrest, heart, brain, emergency, resuscitation, and central nervous system. This search produced approximately 500 publications, which formed the basis for this review. Within this set, most of the publications involved either animal studies or small, human studies.

The greatest difficulty in searching the literature on hypothermia is the nature of the therapy. It is not a single intervention, but rather a combination of various interventions. Variations in inclusion/exclusion parameters, methodologies of cooling, goal temperatures, timing, and outcome measures are a major limitation to synthesizing the evidence.17-19

The results of 2 landmark prospective randomized clinical trials published in 2002 established the foundation for inducing hypothermia in postcardiac arrest patients.11,15 These 2 studies have been used as the basis for many of the recommendations and guidelines published in the last decade. (See Table 1.)

Risk Management Pitfalls For Therapeutic Hypothermia

  1. “A patient has arrived from a nursing home with ROSC after being found unresponsive during the morning shift change. The patient is nonverbal and noninteractive, with little apparent cognitive ability secondary to a prior stroke. Am I obligated to induce hypothermia?” This practice is not the standard of care at this time; thus, the emergency clinician reserves the right to decide on a case-by-case basis which patients may or may not benefit from this therapy. The emergency clinician reserves the right to decide when clinical and/or extraclinical factors (such as resource allocation) make the application impractical.
  2. “I was treating a patient with chest pain and a very concerning history when she suddenly arrested. After several minutes, we were able to bring her back. An ECG taken after the arrest showed lateral wall myocardial infarction. I activated the cath team, but should I have waited until the patient was cooled before letting her go for the procedure?” Treating a patient with induced hypothermia should not delay or inhibit the application of any other emergent procedures or investigations (eg, cardiac catheterization, surgical intervention, interventional radiology) related to the underlying pathology of cardiac arrest. Most times, the interventions can be performed simultaneously.
  3. “As an emergency clinician, I’m excited about the prospect of having an additional therapy for my postcardiac arrest patients. I have all of the tools in my ED and would like to get started right away. What else do I need to do?” Therapeutic hypothermia is a multidisciplinary treatment modality; before initiation of any hypothermia protocol, all potential services that may be caring for the patients should be involved in the discussion. These services may include neurology, intensive care medicine, emergency medicine, and EMS.
  4. “I’m called to the bedside by the nurse because the most recent ECG of a patient receiving therapeutic hypothermia appears to have a lot of artifact that she can’t seem to get rid of. On close inspection, the patient appears to have a fine tremor. The nurse asks if I would like to administer another dose of paralytic.” Paralysis should be used only as a last resort for shivering control, as masking seizure activity may result in worsening of neurologic status despite any benefits gained by therapeutic hypothermia. Sedation and analgesia should be used first.
  5. “While working medical control for my local EMS system, I received a call about a patient postcardiac arrest with ROSC. The EMS providers stated that they had been training to perform hypothermia and asked if they should begin therapy before my assessment of the patient.” Emergency medical services are a vital part of the hypothermia care paradigm, as the therapy has been shown to be more effective when delivered early. The initial cooling process can be started easily in the field with ice or cooled saline. If the receiving emergency clinician does not feel that hypothermia care is warranted, then there is no obligation to continue it.
  6. “The patient receiving therapeutic hypothermia suddenly went into atrial fibrillation. I decided to attempt cardioversion, and the first shock converted the patient to normal sinus rhythm. After several minutes, however, the atrial fibrillation returned. Then the patient’s blood pressure started falling.” The development of a life-threatening arrhythmia is a contraindication to hypothermia care. The patient should be rewarmed to normothermia.
  7. “When using therapeutic hypothermia I continue to have difficulty maintaining a constant temperature. Every time I adjust the device or add saline to recool the patient, I end up overshooting my goal.” First and foremost, check the patient for shivering. Wide temperature swings are not the norm and may be a sign of occult or fine shivering. Second, consider a different placement for the particular feedback device. If possible, esophageal placement should be attempted.
  8. “After several hours of stability during therapeutic hypothermia, my patient became gradually more tachycardic. Although she was initially weaned from pressors, her blood pressure started falling again. I used ultrasound only to find her IVC had collapsed, and her heart was pumping vigorously.” Cold will cause a diuresis. Although all patients may require some form of maintenance fluid, hypothermic patients should have urine output monitored closely and subsequently matched in return.
  9. “While beginning to rewarm the patient, I noticed a change in the T wave morphology on the monitor. A subsequent ECG showed peaked T waves. Did I miss renal failure in the patient?” A too-rapid rate of rewarming will cause severe electrolyte shifts, particularly hyperkalemia. The rate of rewarming should not exceed 1°C (2°F) per hour and ideally should be more toward 0.5°C (1°F) per hour.
  10. “A patient who has undergone hypothermia care is neurologically devastated several days after rewarming. I am asked why it did not work.” Hypothermia care offers no guarantees. Efforts should be made to explain to providers and family that this therapy will increase the patient’s chances for attaining a good neurologic outcome; however, it is difficult to predict which patients will fully recover on the basis of the available data.

Tables and Figures

Table 1. Published Guidelines Specific To Therapeutic Hypothermia


Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available.

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Matthew Constantine

Publication Date

April 2, 2011

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