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Therapeutic hypothermia after cardiac arrest


CARDIAC ARREST outside the hospital kills roughly 250,000 Americans each year. Worldwide, the average survival rate for outof-hospital cardiac arrest is just 6%. And those who survive are at risk for neurologic injury. Historically, only about 20% of cardiac arrest survivors who remained comatose have awakened with a good neurologic outcome.

Therapeutic hypothermia holds out the promise of improving these sobering statistics. This article reviews the physiologic changes that occur during and after cardiac arrest, focusing on how such changes cause neurologic deficits. It identifies the mechanisms, and adverse effects of therapeutic hypothermia and describes how to manage and prevent adverse effects.

Therapeutic hypothermia after cardiac arrest

What is therapeutic hypothermia?

Therapeutic hypothermia (also called targeted temperature management) refers to deliberate reduction of the core body temperature, typically to a range of about 32° to 34° C (89.6° to 93.2° F) in patients who don’t regain consciousness after return of spontaneous circulation following a cardiac arrest. (See Exclusion criteria for therapeutic hypothermia by clicking on the PDF icon above.) Hypothermia also is used to treat newborns with perinatal asphyxia; however, this article focuses on its use in adults.

How does cardiac arrest cause neurologic deficits?

After cardiac arrest, initial neurologic injury occurs when circulatory collapse impairs oxygen flow to the brain. Without oxygen, the brain switches to anaerobic metabolism, which disrupts adenosine triphosphate–dependent cellular pumps, resulting in excessive calcium and glutamate excretion. This excess makes brain cells more excitable, leading to further hypoxemia, in turn causing mitochondrial and cellular death. Cellular death results in cerebral edema, producing further damage. The initial injury also disrupts the blood-brain barrier, which increases fluid in the brain and worsens cerebral edema.

Once circulation is restored, reperfusion injury occurs and may persist for hours. During this time, cell death triggers an inflammatory response in which the immune system releases neutrophils and macrophages to eliminate the dead cells. Unfortunately, this process produces free radicals that cause continued cell damage, worsening the inflammatory response, which exacerbates cerebral edema. This vicious cycle continues to cause neurologic injury.

How does therapeutic hypothermia help?

Hypothermia counteracts neuroexcitation in brain cells by stabilizing calcium and glutamate release, reducing the degree of cell death. It also stabilizes the blood-brain barrier and suppresses the inflammatory process, reducing cerebral edema. Cerebral metabolism decreases 6% to 10% for every degree Celsius that body temperature drops. As cerebral metabolism declines, the brain needs less oxygen.

In essence, hypothermia counteracts many of the destructive mechanisms of cardiac arrest. Its effects resemble those of cardiac defibrillation, which makes the heart stop and then reset itself to a normal rhythm. Similarly, hypothermia halts destructive brain mechanisms and lets the brain reset itself to normal functioning.

Although the medical community has known of hypothermia’s potential benefits for years, this therapy gained support only after the New England Journal of Medicine published two landmark studies in 2002. The Hypothermia After Cardiac Arrest (HACA) study and the Bernard study showed significantly improved neurologic outcomes for the hypothermia group compared to the normothermia group. The HACA study also showed reduced mortality. Both studies included only patients with ventricular tachycardia and ventricular fibrillation.

These studies led the American Heart Association (AHA) to update its cardiopulmonary resuscitation guidelines in 2005 to include a recommendation for therapeutic hypothermia in cardiac-arrest patients who don’t regain consciousness. In 2010, AHA opened the door for implementing therapeutic hypothermia in patients with asystole, pulseless electrical activity, or in-house cardiac arrest, although research hasn’t been completed on these populations.

In 2010, AHA strengthened its position based on a growing body of research. Because therapeutic hypothermia is the only intervention shown to improve neurologic outcome, AHA now advises clinicians to consider therapeutic hypothermia for any patient who can’t follow verbal commands after return of spontaneous circulation. It also recommends transporting cardiac-arrest patients to a facility that can provide therapeutic hypothermia along with coronary reperfusion, advanced neurologic monitoring, and standardized goal-directed care.

Phases of therapeutic hypothermia

Therapeutic hypothermia occurs in three phases—induction, maintenance, and rewarming. Clinicians must control hypothermia and rewarming to prevent potential adverse effects, such as arrhythmias and skin breakdown during the cold phases (induction and maintenance) and rapid electrolyte shifts during the rewarming phase. Temperature should be monitored with a method that measures core temperature, such as use of an esophageal, bladder, or pulmonary artery catheter. (See Body temperature during therapeutic hypothermia phases.)

Induction phase

The goal of the induction phase is to get the patient to target body temperature as quickly as possible. Doing this may entail the use of ice packs, iced lavage, rapid cold-fluid infusion, noninvasive cooling devices (such as cooling blankets, wraps, or gel pads), or an intravascular catheter that circulates cold fluid in a closed loop within a large vein. At our facility, we combine rapid cold-fluid infusion with a noninvasive gel pad system.

Our protocol also calls for sedation and neuromuscular blockade when the cooling process begins, to prevent shivering during induction; this allows rapid cooling to target temperature. Drug selection for neuromuscular blockade varies among formularies; our facility uses cisatracurium. Although studies show the potential for resistance to neuromuscular blockers in patients who’ve received anticonvulsants, we haven’t observed resistance in the more than 400 cases at our facility.

Induction commonly causes mild diuresis. Cold diuresis results from increased venous return stemming from vasoconstriction, decreased antidiuretic hormone levels, and tubular dysfunction, which in turn increase urine output (in some patients, up to several liters in 1 to 2 hours). This underscores the importance of careful fluid-balance monitoring with central venous pressure monitoring and fluid intake and output measurement. Volume replacement may be needed to prevent fluid deficit and hypotension.

Maintenance phase

During the maintenance phase, controlling the patient’s temperature within the target range (usually 32° to 34° C) is crucial. This phase can last up to 24 hours from the time the target temperature is reached (depending on facility protocol). Automated invasive and noninvasive methods can be used to keep the patient within range; these methods are much less labor-intensive than nonautomated methods.

Rewarming phase

Temperature control remains important during rewarming. Warming the patient too quickly or allowing continued shivering causes dangerous electrolyte shifts, leading to potentially lethal arrhythmias. Controlled rewarming of 0.15° to 0.5° C per hour is recommended. To maintain tight temperature control throughout rewarming, our protocol calls for a neuromuscular blockade.

Because electrolytes shift out of the cells back into the serum during rewarming, frequent electrolyte monitoring is needed during this phase to prevent critically elevated levels. Slow, controlled rewarming allows the kidneys to excrete excess potassium, preventing hyperkalemia.

The patient may become hypoglycemic during rewarming as the insulin resistance of earlier hypothermia phases diminishes. Glucose levels must be monitored frequently, with insulin titration and dextrose boluses used as needed to maintain the patient within ordered ranges.

Careful fluid monitoring during rewarming is crucial because of the vasodilation that accompanies a body temperature rise. Volume replacement may be needed to prevent fluid deficit and hypotension.


Duration of therapeutic hypothermia depends on facility protocol. No research is available on optimal duration. Some facilities start counting duration from the time cooling begins; others start when the patient reaches target temperature.

Potential adverse effects

Therapeutic hypothermia may lead to fluid and electrolyte imbalances, arrhythmias, insulin resistance, shivering, coagulation problems, and other adverse effects. (See Preventing and managing adverse effects by clicking the PDf icon above.)

Fluid and electrolyte imbalances

Fluid and electrolyte shifts (especially of potassium, magnesium, and calcium) are common with therapeutic hypothermia. During the induction and maintenance phases, electrolytes shift intracellularly. Careful electrolyte monitoring and replacement are crucial to maintain normal electrolyte levels and prevent potential arrhythmias.


Bradycardia, atrioventricular blocks, and atrial and ventricular fibrillation may occur. Although hypothermia may render atropine ineffective in bradycardia, transcutaneous or transvenous pacing can be used to treat symptomatic bradycardia. For other symptomatic arrhythmias, treatment is the same as for other critical-care patients.

Insulin resistance

Therapeutic hypothermia causes insulin resistance, commonly leading to hyperglycemia, which increases the infection risk. Standardized glucose monitoring and insulin administration can help control hyperglycemia.


The body’s natural defense mechanism against cold, shivering increases metabolic activity and enhances oxygen consumption and rewarming.

Adequate sedation and counterwarming of extremities helps control shivering. Using a neuromuscular blockade during induction and rewarming can tightly control the patient’s temperature and avoid shivering. During the maintenance phase, a bolus dose of neuromuscular blockers may be given if shivering or microshivering (subclinical muscle tone) occurs. Managing and preventing shivering promote tight temperature control, keeping the patient within the target range and decreasing the risk of arrhythmias that can arise if body temperature drifts below 30° C (86° F).

At our facility, we’ve found that avoiding shivering is crucial to effective temperature control. In our experience, if shivering induces warming and isn’t treated early, late use of a neuromuscular blockade to control shivering can lead to overshooting below the target temperature range of 32° to 34° C.

Coagulation problems

Mild platelet dysfunction may arise during hypothermia, increasing the bleeding risk. Most patients don’t exhibit bleeding problems other than oozing from central or other invasive lines. If bleeding problems occur, some facilities increase the target temperature on the cooling device from 33° to 34° C, which alleviates most platelet dysfunction occurring below 34° C. Blood products may be given. The clinical team must monitor coagulation studies and determine trends.

Pain and sedation management

Pain and sedation management poses unique challenges. Being cold isn’t comfortable, but how do you assess for discomfort in a comatose patient who’s cold? What’s more, hypothermia diminishes the body’s ability to respond to stimulation. So how do you assess the patient’s sedation level? Originally, we used bispectral index monitors but found them less reliable in hypothermic than normothermic patients. However, continuous electroencephalographic (EEG) monitoring can be used to monitor the sedation level and detect seizures.

Evaluating the level of neuromuscular blockade also is difficult in hypothermic patients. Train-of-four monitoring routinely is used in patients receiving neuromuscular blockers to stimulate twitching and allow evaluation of the blockade level. But in hypothermia, intracellular electrolyte shifts and the cold itself can make train-of-four monitoring less accurate. Several researchers have found that cooling slows nerve conduction, so train-of-four monitoring at temperatures used for therapeutic hypothermia isn’t reliable.

To complicate matters, hypothermia affects drug metabolism in several ways. Studies show reduced clearance of some drugs commonly used in intensive-care patients undergoing therapeutic hypothermia—epinephrine, norepinephrine, morphine, fentanyl, propofol, midazolam, barbiturates, rocuronium, vecuronium, phenytoin, nitrates, and certain beta blockers. Hypothermia-induced changes in volume and renal function may play a part in drug metabolism. Given these potential physiologic responses to hypothermia, use of lower dosages of sedatives and neuromuscular blockers may be possible. Keep in mind that although sedation, analgesia, and neuromuscular blockade are recommended during therapeutic hypothermia, the best sedation-analgesia protocol is unknown.

Determining prognosis

Determining the patient’s neurologic prognosis is difficult. Although studies on neurologic assessment for prognostication in cardiac arrest have been done, they didn’t involve patients who’d received therapeutic hypothermia. (See Tracking outcomes and trends by clicking the PDF icon above.)

Nursing care

Nurses play a vital role in preventing, detecting, and treating adverse effects and complications of therapeutic hypothermia. Nearly all adverse effects can be prevented or managed in an intensive-care setting.

Care for patients receiving therapeutic hypothermia can be highly complex and require intensive nursing monitoring. Many require multiple vasopressors, antiarrhythmics, insulin therapy, and electrolyte replacement. Other concurrent supportive treatments may include an intra-aortic balloon pump, continuous renal replacement therapy, and prone patient positioning.

Therapeutic hypothermia suppresses the inflammatory response, increasing the risk of infection. Ensure scrupulous hand hygiene and provide meticulous care to prevent hospital-acquired infections, such as catheter-associated bloodstream infections, ventilator-acquired pneumonia (VAP), and catheter-associated urinary tract infections. Hypothermia patients are vulnerable to aspiration and VAP because hypothermia impairs respiratory ciliary function and decreases gastric motility. To help prevent VAP, use such practices as appropriate oral care, suctioning, and head-of-bed elevation higher than 30 degrees.

Vasoconstriction caused by hypothermia can lead to skin breakdown. Assess the patient’s skin frequently to detect problems early. To help prevent breakdown, use preventive measures, such as a low-airloss bed and waffle boots.

As described earlier, neurologic assessment presents challenges. The need for adequate sedation and neuromuscular blockade to control shivering—and hypothermia itself—can complicate standard neurologic assessment. Our facility uses continuous EEG monitoring to help determine if the patient has any level of awareness. Be aware, too, that once the patient is normothermic, sedatives and neuromuscular blockers may take time to clear the body because of hypothermia’s effect on drug metabolism.

Be sure to provide family support and education. Cardiac arrest occurs suddenly and usually without warning. Family members may be overwhelmed by the thought that their loved one is critically ill and attached to machines, as well as by the amount of activity and clinicians involved in the patient’s care. To reduce their anxiety, explain the equipment, tests, monitoring, and procedures. They may express concern that their loved one is cold to the touch; teach them the reasons for therapeutic hypothermia and how long it will last. Reassure them that sedation and analgesia are being used to ease patient discomfort. Advise them that therapeutic hypothermia can improve outcomes after cardiac arrest. Explain that the goal is for the patient to emerge from therapeutic hypothermia neurologically intact, without complications of critical illness.

Selected references

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(8):557-563.

Centers for Disease Control and Prevention. Healthcare-associated infections. Accessed May 11, 2011.

Chamorrow C, Borrallo JM, Romera MA, et al. Anesthesia and analgesia protocol during therapeutic hypothermia after cardiac arrest: a systematic review. Anesth Analg. 2010;110(5):1328-1335.

EEC 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(suppl 24):IV1-203.

Heier T, Caldwell JE. Impact of hypothermia on the response to neuromuscular blocking
drugs. Anesthesiology. 2006;104(5):1070-1080.

The 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.

Nunnally ME, Jaeschke R, Bellingan GJ, et al. Targeted temperature management in critical
care: a report and recommendations from five professional societies. Crit Care Med.

Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010
American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Circulation. 2010;122(18 suppl 3):S768-786.

Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia.
Crit Care Med. 2009;37(suppl 7):S186-S202.

Qadir R, Kanjwal K. Severe bradycardia with a prominent J wave refractory to atropine:
was it a cause or a result of a fall? A case report and a brief review on the treatment of
hypothermia. Am J Ther. 2010;17(2):223-225.

Michelle E. Deckard is a clinical nurse specialist at Indiana University Health/Methodist Hospital in Indianapolis. Patricia R. Ebright is an associate professor in the Department of Adult Health at Indiana University School of Nursing in Indianapolis. Deckard has been aWebcast presenter for Medivance, Inc. This article was peer-reviewed for bias and none was found. Ebright and the planners of this CNE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.


  • E. James Arnold
    October 18, 2022 8:53 am

    Thanks for writing this . I survived 70+ minutes of SCA in 2016. Arrythmic mitral valve was probable trigger for sca
    I was brought to elmhurst hospital where they induced a three day thermal coma. I am 6.5 years past this event. I am grateful for this technology and it has been a steady recovery. Most follow up has been with cardio health .I am following up on neuro screenings. My outcome of success in survival was with such long odds. I think the thermal coma helped me a great deal. In memory of this i have some confusion in how to seperate memory of when i was in sca versus the memory of the time spent in the coma. There is a lot of recent advocacy tonlearn cpr and ,learn aed . But the next steps treatment to sudden cardiac arrest is not so oftern talked about. Thank You for making this article .:)

  • Dr. Rajesh M. Buddhadev
    November 11, 2019 7:28 am

    It gives excellent Scientific as well as wonderful general information also.
    It clears many doubts in our mind also.

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  • Supplement post. The article has a lot of good information. It is related to the situation of which I am involved. Dale Cook

  • This beautifully complete article reminds me the debt of gratitude I owe to the RNs who made this possible for me.
    I died in a car, 3 blocks from St. Luke’s Northland in Kansas City 20 months ago.
    What they did, how they did it places me in a rare class of humans.
    Thank you, authors.
    Dan Verbeck

  • nice post thanks for sharing

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