Elsevier

Resuscitation

Volume 70, Issue 3, September 2006, Pages 369-380
Resuscitation

Review paper
Therapeutic hypothermia

https://doi.org/10.1016/j.resuscitation.2006.01.017Get rights and content

Summary

Therapeutic hypothermia has been used for millennia, but in recent years was not in much clinical use due to an apparent high risk of complications. More recently, the benefits of induced therapeutic hypothermia have been rediscovered, mainly with the improvement in neurological outcome in out-of-hospital cardiac arrest victims. In addition, therapeutic hypothermia has been suggested to improve outcome in other neurological conditions such as traumatic brain injury, neonatal asphyxia, cerebrovascular accidents and intracranial hypertension. This article reviews the history of the discovery of therapeutic hypothermia, as well as the current therapeutic applications and ways to deliver this treatment. Cooling techniques and recovery processes, as well as potential complications are also reviewed. Clinicians caring for a wide variety of critically ill patients should be familiar with the use of therapeutic hypothermia.

Introduction

The use of therapeutic hypothermia over the past few years has increased worldwide. This technique has proven advantageous in a variety of clinical settings. For several decades, therapeutic hypothermia had been used in an attempt to provide anesthesia during amputations, to prevent cancer cells from multiplying and to reduce complications during heart surgery.1, 2 The use of mild therapeutic hypothermia after cardiac arrest was first described in the 1950s, but was soon abandoned without being formally tested.3, 4, 5 However, over the last decade, many animal and clinical trials have described the beneficial effects of lowering the body's core temperature in a variety of situations.5 Indeed, therapeutic hypothermia lowers the cerebral metabolic rate in anoxic brain injury and in cardiac arrest.6 Therapeutic hypothermia has been shown to have a protective effect during cardiac and intracranial surgical procedures, where blood flow to the brain needs to be interrupted.7 Therapeutic hypothermia has also been used in head-injured patients for the control of increased intracranial pressure that is refractory to hyperventilation, osmotherapy, ventricular drainage and barbiturates.8 In November 2005, the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation recommended therapeutic hypothermia in unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest when the initial rhythm was ventricular fibrillation.4, 9, 10, 11, 12 The Committee encouraged further research to expand the indications for therapeutic hypothermia to in-hospital cardiac arrests and perinatal asphyxia.

Section snippets

Historical aspects of hypothermia as a treatment

Hypothermia has been used for centuries for a variety of reasons.13 However, the use of cold temperatures in modern clinical medicine is probably only 200 years old. The Russian method of resuscitation, described in 1803, consisted in covering a patient with snow hoping for return of spontaneous circulation (ROSC).13 Therapeutic hypothermia was used during Napoleon's Russian campaign in 1812, by the surgeon Baron de Larrey attempting to preserve injured limbs, as well as for its anesthetic

Pathophysiology of cerebral ischemia and mechanisms and effects of therapeutic hypothermia

Cerebral injury occurs after any condition in which there is inadequate blood flow to the brain for more than 5 min.5, 28 Cerebral ischemia produces a cascade of effects including ATP energy depletion, ion pump failure, release of free radicals and excitotoxic agents such as glutamate and calcium5, 23, 27, 29, 30 (see Figure 1).

These post-ischemic effects are exacerbated when the patient's temperature increases 0.5 °C or more above 37 °C.31, 32, 33, 34 In fact, the formation of free radicals and

Timing and therapeutic window for therapeutic hypothermia

The extent of anoxic brain damage is related mainly to the duration of ischemia, 5 min being the tolerance limit for complete anoxia.53, 54 For this reason, the vast majority of investigators believe that hypothermia should be induced as early as possible.11, 53 Safar and colleagues conducted several animal studies demonstrating the beneficial effects of mild-to-moderate therapeutic hypothermia induced very early after survival from cardiac arrest.30, 55, 56 The earlier therapeutic hypothermia

Conventional and innovative cooling techniques

There are several ways to induce therapeutic hypothermia31, 64 (see Table 1). Among them, the most commonly used include: surface cooling and invasive cooling. Surface cooling is relatively simple to use, but takes between 2 and 8 h to reduce core body temperature.11, 38 It can be accomplished by the use of circulating cold-water blankets and cold air-forced blankets, the former being the most frequently used32, 64, 65 (see Figure 2). Less sophisticated methods, such as ice packs and cold-water

Monitoring core temperature

There are several levels of therapeutic hypothermia: mild at 34–36 °C, moderate at 28–32 °C, deep at 17–27 °C, profound at 4–16 °C.25, 26 Induced hypothermia is recommended at 32–34 °C for most therapeutic purposes.11

A reliable, continuous temperature measurement and a tight control with minimal variations is essential for therapeutic hypothermia.77 It is important to take into consideration that brain temperature may be dissociated from the systemic temperature by 0.2–0.1 °C.26 Monitoring of the

Practical considerations during therapeutic hypothermia

Shivering is the primary side effect of therapeutic hypothermia and may increase the metabolism at a cellular level.11 It increases acidosis and increases sympathetic discharge.8 For this reason, sedation and neuromuscular blocking agents are recommended by some authors.32 In particular, intravenous meperidine (pethidine) alone or with oral buspirone have been used in therapeutic hypothermia as these agents reduce the shivering threshold, while causing little sedation or respiratory toxicity.32

Rewarming

Rewarming after therapeutic hypothermia should be activated with the use of heating air blankets, allowing the core temperature to rise at 0.5–1 °C per hour.6 During this time, shivering should continue to be suppressed as temperature increases. Intravenous fluid infusion may be helpful to maintain the mean arterial blood pressure as some patients may have sudden vasodilation upon rewarming.6 In some instances, for example when hypothermia needs to be prolonged to keep a controlled intracranial

Current indications for therapeutic hypothermia

Based on published evidence, an advisory statement by the Advanced Life Support (ALS) Task Force of the International Liaison Committee on Resuscitation was issued in November 2005 announcing recommendations for the use of therapeutic hypothermia.4, 9, 10, 11, 12 This panel's indications for therapeutic hypothermia included: unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest,4, 9, 10, 11, 12 with recommended cooling to 32–34 °C for 12–24 h when the

Complications of therapeutic hypothermia

Several studies have reported complications with the use of therapeutic hypothermia particularly at lower temperatures (<32 °C) and with an uncontrolled maintenance of temperature. Among these, dysrhythmias, infections and primary coagulopathy are the most commonly noted.11, 12 The hypothermia after cardiac arrest (HACA) study group reported sepsis as the main complication with hypothermia, however, this did not reach statistical significance.5

Some authors recommend avoiding therapeutic

The future

Based on preliminary studies, the use of therapeutic hypothermia is likely to be expanded to many other clinical scenarios. Guidelines will be implemented favoring a greater number of patients to achieve a good neurological outcome after anoxic brain injury of different etiologies.

In fact, the recommendations from International Liaison Committee on Resuscitation foreshadow the beneficial potential of therapeutic hypothermia for in-hospital cardiac arrest and for other initial rhythms after

Conclusions

Evidence-based medicine indicates that moderate degree of selective brain cooling, if instituted promptly, may protect against ischemic neuronal injury of the type that occurs commonly following a cardiac arrest. Therapeutic hypothermia is now seen as a new neuroprotective strategy and is gaining ground as an emergency therapy. The best cooling technique is one that is easy to use and at the same time effective. Further studies and clinical trials have to be done for a fuller understanding of

Conflict of interest

The authors disclose no conflict of interest in the research orientation, elaboration and proofreading of this article. Our article is not biased towards any particular belief or point of view. The authors did not receive any kind of monetary remuneration or grants for the preparation of this article. The purpose of this article is to provide the scientific and medical evidence regarding the use of therapeutic hypothermia. In no way, the authors’ intention is to persuade the audience to

References (101)

  • E.J. Lawrence et al.

    Neuroprotection with delayed initiation of prolonged hypothermia after in vitro transient global brain ischemia

    Resuscitation

    (2005)
  • I. Virkkunen et al.

    Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringer's solution: a pilot study

    Resuscitation

    (2004)
  • A. Kliegel et al.

    Cold simple intravenous infusions preceding special endovascular cooling for faster induction of mild hypothermia after cardiac arrest: a feasibility study

    Resuscitation

    (2005)
  • S. Bernard et al.

    Induced hypothermia using large volume, ice-cold intravenous fluid in comatose survivors of out-of-hospital cardiac arrest: a preliminary report

    Resuscitation

    (2003)
  • J.P. Bryk et al.

    Deep brain hypothermia by means of high-flow biventricular cooling

    Resuscitation

    (1976/1977)
  • S.S. Yang et al.

    Cold perfluorochemical-induced hypothermia protects lung integrity in normal rabbits

    Biol Neonate

    (2005)
  • R.M. Zweifler et al.

    Induction and maintenance of mild hypothermia by surface cooling in non-intubated subjects

    J Stroke Cerebrovasc Dis

    (2003)
  • G. Wollenek et al.

    Cold water submersion and cardiac arrest in treatment of severe hypothermia with cardiopulmonary bypass

    Resuscitation

    (2002)
  • J. Villar et al.

    Effects of induced hypothermia in patients with septic adult respiratory distress syndrome

    Resuscitation

    (1993)
  • M.A. Peberdy et al.

    Post-resuscitation care: is it the missing link in the Chain of Survival?

    Resuscitation

    (2005)
  • Y. Mordecai et al.

    Temperature modulation of neuronal injury

  • T. Fay

    Observations on prolonged human refrigeration

    NY State J Med

    (1940)
  • D.W. Benson et al.

    The use of hypothermia after cardiac arrest

    Anesthn Analg

    (1959)
  • S.A. Bernard

    Therapeutic hypothermia after cardiac arrest

    MJA

    (2004)
  • M. Holzer et al.

    The hypothermia after cardiac arrest study group: mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

    N Engl J Med

    (2002)
  • S. Bernard et al.

    Induced hypothermia in critical care medicine: a review

    Crit Care Med

    (2003)
  • W.G. Bigelow et al.

    Further experiences with hypothermia for intracardiac surgery in monkeys and groundhogs

    Ann Surg

    (1953)
  • S. Tisherman

    Hypothermia and injury

    Curr Opin Crit Care

    (2004)
  • M.F. Hazinski et al.

    Controversial topics from the 2005 International Consensus Conference on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations

    Circulation

    (2005)
  • P.J. Safar et al.

    Therapeutic hypothermic after cardiac arrest

    N Engl J Med

    (2002)
  • L.W. Smith et al.

    Observations on human beings with cancer maintained at reduced temperature of 75–90° Fahrenheit (24–32 °C)

    Am J Clin Pathol

    (1940)
  • T. Fay

    Observations on generalized refrigeration in cases of severe cerebral trauma

    Res Publ Assos Res Nerv Dis

    (1945)
  • H.L. Rosomoff et al.

    Brain volume and cerebral fluid resuscitation during hypothermia

    Am J Physiol

    (1955)
  • H.L. Rosomoff et al.

    Cerebral blood flow and cerebral oxygen consumption during hypothermia

    Am J Physiol

    (1954)
  • J.L. Pool et al.

    Mechanism and control of centrally induce cardiac irregularities during hypothermia. I. Clinical observations

    J Neurosurg

    (1958)
  • V.C. DeGuzman

    Hypothermia: its effects upon hematologic clearance in experimentally induced staphylococcal bacteremia

    Surgery

    (1963)
  • M. Bloch

    Accidental hypothermia

    Br Med J

    (1967)
  • T.L. Smith et al.

    Hypothermia and neurologic outcome in patients following cardiac arrest: should we be not hot to cool off our patients?

    Crit Care

    (2002)
  • A. Zeiner et al.

    Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest

    Stroke

    (2000)
  • S.A. Bernard et al.

    Treatment of comatose survivors of the out-of-hospital cardiac arrest with induced hypothermia

    N Engl J Med

    (2002)
  • V.A. Negovsky

    Postresuscitation disease

    Crit Care Med

    (1988)
  • U.M. Illievich et al.

    Effects of hypothermia metabolic suppression on hippocampal glutamate concentrations after transient global cerebral ischemia

    Anesth Analg

    (1994)
  • P. Safar

    Resuscitation of the ischemic brain

  • M.N. Diringer

    Treatment of fever in the neurologic intensive care unit with a catheter-based heat exchange system

    Crit Care Med

    (2004)
  • D.D. Bell et al.

    Management following resuscitation from cardiac arrest: recommendations from the 2003 Rocky Mountain Critical Care Conference

    Can J Anesth

    (2005)
  • M.N. Diringer et al.

    Elevated body temperature independently contributes to increased length of stay in neurologic intensive care unit patients

    Crit Care Med

    (2004)
  • A. Zeiner et al.

    Hypothermia after cardiac arrest is associated with an unfavorable neurologic outcome

    Arch Intern Med

    (2001)
  • R.C. Baena et al.

    Hypothermia delayed by 24 hours aggravates neuronal damage in rat hippocampus following global ischemia

    Neurology

    (1997)
  • C. Coimbra et al.

    Long-lasting neuroprotective effect of postischemic hypothermia and treatment with an anti-inflammatory/antipyretic drug

    Stroke

    (1996)
  • P. Vaagenes et al.

    Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms

    Crit Care Med

    (1996)
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    A Spanish translated version of the summary of this article appears as Appendix in the online version at doi:10.1016/j.resuscitation.2006.01.017

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