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...ore than 375,000 individuals per year in Europe [de Vreede-Swagemakers et al. 1997], while it carries a greater than 90% mortality rate, leading to over 300,000 deaths in the United States each year [=-=Thom et al. 2006-=-]. Despite the development of pharmacologic therapies for CA and the improved access to electrical defibrillation this mortality rate has not declined significantly over the past few decades. Cardiopu...

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...]. However, there were several studies where the control of ICP was not related with improved functional outcome, something that was attributed to rapid posthypothermic rewarming [Alzaga et al. 2006; =-=Bernard and Buist, 2003-=-]. The results of these studies emphasize that, if hypothermia is used to manage intracranial hypertension, rewarming must be accomplished slowly and, ideally, over the course of 1224h or more, other...

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...rotection was attained when hypothermia was induced at 1, 6, or 12 hours after reperfusion and preserved for 48 hours, while neuroprotection was impaired when the commencement of therapy was delayed [=-=Colbourne et al. 1999-=-]. In another animal (swine) study, extracorporeal venovenous cooling has been tested as a thriving procedure to rapidly induce MTH [Holzer et al. 2005a]. There are no studies comparing early versus d...

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...diac arrest A number of landmark studies and a meta-analysis have demonstrated that cooling patients can provide significant survival benefit after initial resuscitation from CA [Holzer et al. 2005b; =-=Bernard et al. 2002-=-; HACA Study Group 2002; Hachimi-Idrissi et al. 2001]. The European HACA (Hypothermia After Cardiac Arrest) trial group demonstrated an improvement in survival to hospital discharge with favorable neu...

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...receive optimal ICU care such as frequent turning, oral care every 24 hours, ventilator bundling interventions, glucose level control, peptic ulcer prophylaxis, and deep vein thrombosis prophylaxis [=-=Arrich, 2007-=-]. The treatment involves sedation and mechanical ventilation (PO2 90100mmHg) with a temperature goal of 3234C within 26 hours [ECC Committee, Subcommittees and Task Forces of the American Heart A...

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... 15 minutes of ROSC, when cooling is maintained for only a short duration (12 hours), might be even better. However, this has not yet been shown clinically [Abella et al. 2004; Kuboyama et al. 1993; =-=Sterz et al. 1991-=-]. No differences in neuroprotection were recorded in a rat model of CA when a 24-hour period of cooling was either initiated at the time of ROSC or delayed by 1 hour [Hicks et al. 2000]. In contrast,...

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...erve and restore the at-risk neurons in the penumbra in focal ischemic brain injury. Rewarming appears to be associated with severe intracranial pressure elevation and brain edema affecting survival [=-=Marion and Bullock, 2009-=-]. The efficacy of therapeutic hypothermia for ischemic stroke has not yet been established by definitive prospective randomized clinical trials [Den Hertog et al. 2007; Konstas et al. 2006] and the 2...

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...esuscitation or within 15 minutes of ROSC, when cooling is maintained for only a short duration (12 hours), might be even better. However, this has not yet been shown clinically [Abella et al. 2004; =-=Kuboyama et al. 1993-=-; Sterz et al. 1991]. No differences in neuroprotection were recorded in a rat model of CA when a 24-hour period of cooling was either initiated at the time of ROSC or delayed by 1 hour [Hicks et al. ...

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...hat cooling during resuscitation or within 15 minutes of ROSC, when cooling is maintained for only a short duration (12 hours), might be even better. However, this has not yet been shown clinically [=-=Abella et al. 2004-=-; Kuboyama et al. 1993; Sterz et al. 1991]. No differences in neuroprotection were recorded in a rat model of CA when a 24-hour period of cooling was either initiated at the time of ROSC or delayed by...

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...related complications or which is the best way to rewarm patients. The most favorable depth and duration of hypothermia and the consequence of the rewarming rate on neurological recovery are unknown [=-=Janata and Holzer, 2009-=-]. The optimal strategy is probably to keep it simple and safe without forgetting that only systematic treatment protocols improve outcomes in post-CA syndrome. The encouraging results of different re...

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...al. 2005]. It has been proposed that for out-ofhospital CAs, victim cooling should be started as soon as possible, ideally at the scene of the arrest by the ambulance crew [Kämäräinen et al. 2008; =-=Kim et al. 2007-=-]. Numerous internal cooling techniques and external or surface cooling devices (Table 3) alone or in combination with the above measures have been described for inducing mild hypothermia [Angus and M...

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...ypertension, rewarming must be accomplished slowly and, ideally, over the course of 1224h or more, otherwise sudden vasodilation leads to rebound increases in intracranial pressure [Gal et al. 2002; =-=Clifton et al. 2001-=-]. Unresolved issues concerning the use of therapeutic hypothermia in CA remain regarding patient selection (children, neonates), optimal timing, duration and depth of cooling, CA extent at the time o...

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...and Task Forces of the American Heart Association, 2005; Holzer et al. 2005b]. During endovascular cooling, skin warming with the utilization of forced-air blankets has effectively reduced shivering [=-=Guluma et al. 2006-=-]. All of these processes represent a treatment protocol that is not difficult to apply to populations who suffer out-of-hospital CA (Table 4). Potential and frequent complications (Table 5) of mild-t...

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...applicable in patients with cardiogenic shock [Skulec et al. 2008]. Hovdenes and colleagues also documented the safety of mild hypothermia in patients in shock after successful resuscitation from VF [=-=Hovdenes et al. 2007-=-]. Recently several publications appeared which emphasize the successful application of MTH in patients with ST elevation myocardial infarction, CA and a primary percutaneous coronary intervention (PC...

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...gnify these injury processes [Bouch et al. 2008] (Figure 1). Hypothermia may block a number of these steps and minimize cellular damage by slowing cerebral metabolism in relation to other mechanisms [=-=Soar and Nolan, 2007-=-] (Table 2). These include a reduction in neuronal apoptosis, inhibition of chemical reactions associated with reperfusion injury, alterations in intracellular cation concentrations due to ion pump dy...

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... a meta-analysis have demonstrated that cooling patients can provide significant survival benefit after initial resuscitation from CA [Holzer et al. 2005b; Bernard et al. 2002; HACA Study Group 2002; =-=Hachimi-Idrissi et al. 2001-=-]. The European HACA (Hypothermia After Cardiac Arrest) trial group demonstrated an improvement in survival to hospital discharge with favorable neurological status in cooled patients compared with ht...

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.../kg over 30 minutes after resuscitation from out-of-hospital CA or traditional ice packs placed on the groin and armpits and around the neck and head has been a safe and successful cooling technique [=-=Kim et al. 2005-=-]. This method has been sufficient and effective also in prehospital settings, and has also been studied in combination with endovascular cooling or with ice-water cooling blankets [Kliegel et al. 200...

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...e [Kim et al. 2005]. This method has been sufficient and effective also in prehospital settings, and has also been studied in combination with endovascular cooling or with ice-water cooling blankets [=-=Kliegel et al. 2005-=-; Polderman et al. 2005]. It has been proposed that for out-ofhospital CAs, victim cooling should be started as soon as possible, ideally at the scene of the arrest by the ambulance crew [Kämäräine...

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...ival [Marion and Bullock, 2009]. The efficacy of therapeutic hypothermia for ischemic stroke has not yet been established by definitive prospective randomized clinical trials [Den Hertog et al. 2007; =-=Konstas et al. 2006-=-] and the 2007 American Stroke Associations Guidelines consider therapeutic hypothermia for ischemic stroke to be level IIIb evidence. In patients with traumatic brain injury, there is strong evidence...

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...medicine, critical care, or cardiology had not used it [Abella et al. 2005]. In a similar survey a year later, the percentage of nonusers was 74% in the USA, 69% in Great Britain, and 39% in Finland [=-=Merchant et al. 2006-=-]. A recent survey of Canadian emergency physicians confirmed the above discouraging results reporting that only 50% of them used therapeutic hypothermia in every day practice [Kennedy et al. 2008]. T...

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...ooled to 3234C for at least 1224 hours. Clinical data suggests that it might be beneficial for comatose survivors of in-hospital CA or cardiac arrhythmias other than VF or ventricular tachycardia [=-=Oddo et al. 2008-=-; Sandroni et al. 2007]. However, large randomized studies addressing therapeutic hypothermia in patients with such characteristics have not thus far appeared. The decision to withhold MTH has to bala...

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...l, in combination with (a) management of cardiac arrhythmias (usually bradyarrhythmias), (b) pH maintenance within normal range, (c) monitoring for electrolyte disorders and hyperglycemia prevention [=-=Oddo et al. 2006-=-]. The most important process is to prevent shivering, which is common, principally during the induction phase, leading to warming and increased oxygen consumption [Bernard et al. 2002; HACA Study Gro...

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...et al. 2007]. Numerous internal cooling techniques and external or surface cooling devices (Table 3) alone or in combination with the above measures have been described for inducing mild hypothermia [=-=Angus and Milbrandt, 2006-=-]. These include ice bags, blankets containing circulating coolant Therapeutic Advances in Cardiovascular Disease 4 (5) 326 http://tac.sagepub.comsat PENNSYLVANIA STATE UNIV on February 20, 2016tak.sa...

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...eared. The decision to withhold MTH has to balance risks and benefits in every individual patient. As an example, there is now good evidence that MTH is applicable in patients with cardiogenic shock [=-=Skulec et al. 2008-=-]. Hovdenes and colleagues also documented the safety of mild hypothermia in patients in shock after successful resuscitation from VF [Hovdenes et al. 2007]. Recently several publications appeared whi...

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...balance, and hemodynamic conditions may alter instantly. The optimal rate of rewarming has not been defined clinically, but current practice is to rewarm gradually with a rate of 0.250.5C per hour [=-=Sterz et al. 2003-=-]. Management and potential adverse effects Hypothermia deteriorates immune function leading to an approximately 19% rate of infection as opposed to a 6% rate of normothermic patients [HACA Study Grou...

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...eatment modality. In a recent practice survey addressing the use of hypothermia after CA in the USA, 87% of the responders practicing emergency medicine, critical care, or cardiology had not used it [=-=Abella et al. 2005-=-]. In a similar survey a year later, the percentage of nonusers was 74% in the USA, 69% in Great Britain, and 39% in Finland [Merchant et al. 2006]. A recent survey of Canadian emergency physicians co...

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...ast few decades. Cardiopulmonary resuscitation restores the return of spontaneous circulation (ROSC) in about 100,000 patients a year in the US while 60% of these die from neurological complications [=-=Booth et al. 2004-=-]. Post-CA syndrome represents a complex interaction of underlying pathologies including brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, unresolved pathologic process lea...

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...e the lack of publications, the use of MTH can be encouraged after ROSC in cardiac surgical settings, as cardiac surgical teams are already familiar with various aspects of hypothermia and rewarming [=-=Chakravarthy, 2009-=-]. Considerable clinical evidence has demonstrated the safety and feasibility of cooling of patients after large strokes [Jian et al. 2003]. Hypothermia reduces the volume of infarct and may preserve ...

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...ROSC and if performed by emergency medical personnel [Nolan et al. 2005; Bernard et al. 2002]. Hyperthermia should be averted as it is a major cause of severe neurological impairment in CA survivors [=-=Cushman et al. 2007-=-]. Based on the initial studies a number of contraindications to MTH are listed in the current literature. These include systemic infection, cardiogenic shock, coagulation disorders (previous thrombol...

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...a et al. 1993; Sterz et al. 1991]. No differences in neuroprotection were recorded in a rat model of CA when a 24-hour period of cooling was either initiated at the time of ROSC or delayed by 1 hour [=-=Hicks et al. 2000-=-]. In contrast, in a gerbil forebrain ischemia model, constant neuroprotection was attained when hypothermia was induced at 1, 6, or 12 hours after reperfusion and preserved for 48 hours, while neurop...

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...apeutic hypothermia (MTH) could improve cardiological and neurological outcome in patients who suffered CA, while MTH side effects could be managed successfully in modern intensive care units (ICUs) [=-=Krause et al. 1986-=-]. Therapeutic hypothermia after cardiac arrest A number of landmark studies and a meta-analysis have demonstrated that cooling patients can provide significant survival benefit after initial resuscit...

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...This method has been sufficient and effective also in prehospital settings, and has also been studied in combination with endovascular cooling or with ice-water cooling blankets [Kliegel et al. 2005; =-=Polderman et al. 2005-=-]. It has been proposed that for out-ofhospital CAs, victim cooling should be started as soon as possible, ideally at the scene of the arrest by the ambulance crew [Kämäräinen et al. 2008; Kim et a...

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...tive cooling techniques such as intracardiopulmonary resuscitation hypothermia with and without volume loading are currently under experimental investigation and have already shown promising results [=-=Yannopoulos et al. 2009-=-]. Better understanding of the pathophysiology of resuscitation and the injury processes on which hypothermia acts and supporting critical and emergency care provider’s participation to encourage guid...

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...on and Bullock, 2009]. However, there were several studies where the control of ICP was not related with improved functional outcome, something that was attributed to rapid posthypothermic rewarming [=-=Alzaga et al. 2006-=-; Bernard and Buist, 2003]. The results of these studies emphasize that, if hypothermia is used to manage intracranial hypertension, rewarming must be accomplished slowly and, ideally, over the course...

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...eperfusion’ injury. This is believed to result from interruption of blood flow (ischemia) while unrestrained reperfusion (return of blood flow after resuscitation) may magnify these injury processes [=-=Bouch et al. 2008-=-] (Figure 1). Hypothermia may block a number of these steps and minimize cellular damage by slowing cerebral metabolism in relation to other mechanisms [Soar and Nolan, 2007] (Table 2). These include ...

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...ms are associated with brain damage during and after CA and subsequent resuscitation. A temporary phase of interrupted or limited cerebral blood flow is followed by rapid or delayed cell reperfusion [=-=Froehler and Romergryko, 2007-=-]. Neurological injury and mortality after ROSC may be due in part to this ‘ischemiareperfusion’ injury. This is believed to result from interruption of blood flow (ischemia) while unrestrained reper...

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...ge intracranial hypertension, rewarming must be accomplished slowly and, ideally, over the course of 1224h or more, otherwise sudden vasodilation leads to rebound increases in intracranial pressure [=-=Gal et al. 2002-=-; Clifton et al. 2001]. Unresolved issues concerning the use of therapeutic hypothermia in CA remain regarding patient selection (children, neonates), optimal timing, duration and depth of cooling, CA...

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...familiar with various aspects of hypothermia and rewarming [Chakravarthy, 2009]. Considerable clinical evidence has demonstrated the safety and feasibility of cooling of patients after large strokes [=-=Jian et al. 2003-=-]. Hypothermia reduces the volume of infarct and may preserve and restore the at-risk neurons in the penumbra in focal ischemic brain injury. Rewarming appears to be associated with severe intracrania...

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...ecently several publications appeared which emphasize the successful application of MTH in patients with ST elevation myocardial infarction, CA and a primary percutaneous coronary intervention (PCI) [=-=Kurisu et al. 2009-=-; Wolfrum et al. 2008]. This proved to be safe and practical as it was attained without delaying door-to-balloon time [Wolfrum et al. 2008]. Despite the lack of publications, the use of MTH can be enc...

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...or at least 1224 hours. Clinical data suggests that it might be beneficial for comatose survivors of in-hospital CA or cardiac arrhythmias other than VF or ventricular tachycardia [Oddo et al. 2008; =-=Sandroni et al. 2007-=-]. However, large randomized studies addressing therapeutic hypothermia in patients with such characteristics have not thus far appeared. The decision to withhold MTH has to balance risks and benefits...

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...r results in the treatment of critical patients. Sayre and colleagues have recently shown that the application of MTH according to the 2005 AHA guidelines improves the neurological outcomes after CA [=-=Sayre et al. 2009-=-]. A recent well-designed review study with MTH patients found that they were more likely to leave hospital without major brain damage and they were more likely to survive to hospital discharge [Arric...

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... thermo-pooling effect Therapeutic Advances in Cardiovascular Disease 4 (5) 328 http://tac.sagepub.comsat PENNSYLVANIA STATE UNIV on February 20, 2016tak.sagepub.comDownloaded fromshypothermic heart [=-=Schwarz et al. 2003-=-]. Intracellular movements of potassium, magnesium, and phosphate during hypothermia lead to unpredictable changes in the mode of action potential and drugcardiomyocyte interactions. Of late, animal ...

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...dverse events were reported. In several countries, many efforts have been made to improve resuscitation treatments and incorporate MTH successfully in resuscitation protocols [Castrejón et al. 2009; =-=Takeuchi et al. 2009-=-]. Innovative cooling techniques such as intracardiopulmonary resuscitation hypothermia with and without volume loading are currently under experimental investigation and have already shown promising ...

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... mode of action potential and drugcardiomyocyte interactions. Of late, animal models researching the impact of hypothermia after rewarming have shown that drug metabolism is successfully normalized [=-=Tortorici et al. 2009-=-]. Myocardial ischemia and severe rebound hyperthermia may also occur. Recently, life-threatening recurrence of ventricular fibrillation has been reported if cooling commences rapidly after ROSC and i...