Neonatal Induced Hypothermia

Neonatal induced hypothermia is a new treatment option for term and near-term infants who have experienced a significant neurologic insult in the perinatal period. Induced hypothermia lowers the core temperature of the brain by 2°C to 5°C. This treatment, when initiated within 6 hours after birth and maintained for 72 hours, lowers the metabolic demands of the brain and therefore reduces the damage from hypoxemia-ischemia and subsequent reperfusion injury. This therapy has been shown in recent studies to reduce the incidence of death and disability in infants with hypoxic-ischemic encephalopathy.     

Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury.

Programmed cell death (apoptosis) is a normal process in the developing nervous system. Recent data suggest that certain features seen in the process of programmed cell death may be favored in the developing versus the adult brain in response to different brain injuries. In a well characterized model of neonatal hypoxia-ischemia, we demonstrate marked but delayed cell death in which there is prominent DNA laddering, TUNEL-labeling, and nuclei with condensed chromatin. Caspase activation, which is required in many cases of apoptotic cell death, also followed a delayed time course after hypoxia-ischemia. Administration of boc-aspartyl(OMe)-fluoromethylketone, a pan-caspase inhibitor, was significantly neuroprotective when given by intracerebroventricular injection 3 h after cerebral hypoxia-ischemia. In addition, systemic injections of boc-aspartyl(OMe)-fluoromethylketone also given in a delayed fashion, resulted in significant neuroprotection. These findings suggest that caspase inhibitors may be able to provide benefit over a prolonged therapeutic window after hypoxic-ischemic events in the developing brain, a major contributor to static encephalopathy and cerebral palsy.     

Therapeutic hypothermia for management of neonatal asphyxia: what nurses need to know

Birth asphyxia can induce a cascade of reactions that result in altered brain function known as hypoxic-ischemic encephalopathy. Possible outcomes for survivors of birth asphyxia vary widely, from a normal outcome to death, with a wide range of disabilities in between, including long-term neurodevelopmental disability, cerebral palsy, neuromotor delay, and developmental delay. Treatment of hypoxic-ischemic encephalopathy has centered on dampening or blocking the biochemical pathways that lead to death of neuronal cells. The reduction of body temperature by 3oC to 5oC less than normal body temperature can reduce cerebral injury. At Mount Sinai Hospital in Toronto, Ontario, the goal of therapeutic hypothermia is to achieve a rectal temperature of 33oC to 34oC, and the protocol is started within 6 hours after birth. The hypothermia is maintained for 72 hours, and then the infant is gradually warmed to normal body temperature (36.8oC-37oC). The protocol and nursing implications are presented.     

Neonatal brain hypothermia

The neonatal brain hypothermia is one of the effective therapies for neonatal hypoxic-ischemic encephalopathy (HIE). The brain hypothermia is thought to protect the brain from the secondary energy failure after hypoxic-ischemic injury at asphyxia. Some literature wrote the effect for neuronal protection for HIE, but the effect is insufficient for severe one. In severe HIE, the basal ganglia regions are injured with ischemic change in the brain MRI findings and occurred the severe permanent handicaps. I think that the reason for fragile of basal ganglia region are related to the existence of NMDA receptor. So, we have to study and develop the new strategy for neuronal protection in HIE.     

Posttraumatic hypothermia is neuroprotective in a model of traumatic brain injury complicated by a secondary hypoxic insult.

OBJECTIVE: Human traumatic brain injury frequently results in secondary complications, including hypoxia. In previous studies, we have reported that posttraumatic hypothermia is neuroprotective and that secondary hypoxia exacerbates histopathologic outcome after fluid-percussion brain injury. The purpose of this study was to assess the therapeutic effects of mild (33 degrees C) hypothermia after fluid-percussion injury combined with secondary hypoxia. In addition, the importance of the rewarming period on histopathologic outcome was investigated. DESIGN: Prospective experimental study in rats. SETTING: Experimental laboratory in a university teaching hospital. INTERVENTION: Intubated, anesthetized rats underwent normothermic parasagittal fluid-percussion brain injury (1.8-2.1 atmospheres) followed by either 30 mins of normoxia (n = 6) or hypoxic (n = 6) gas levels and by 4 hrs of normothermia (37 degrees C). In hypothermic rats, brain temperature was reduced immediately after the 30-min hypoxic insult and maintained for 4 hrs. After hypothermia, brain temperature was either rapidly (n = 6) or slowly (n = 5) increased to normothermic levels. Rats were killed 3 days after traumatic brain injury, and contusion volumes were quantitatively assessed. MEASUREMENTS AND MAIN RESULTS: As previously shown, posttraumatic hypoxia significantly increased contusion volume compared with traumatic brain injury-normoxic animals (p <.02). Importantly, although posttraumatic hypothermia followed by rapid rewarming (15 mins) failed to decrease contusion volume, those animals undergoing a slow rewarming period (120 mins) demonstrated significantly (p <.03) reduced contusion volumes, compared with hypoxic normothermic rats. CONCLUSIONS: These data emphasize the beneficial effects of posttraumatic hypothermia in a traumatic brain injury model complicated by secondary hypoxia and stress the importance of the rewarming period in this therapeutic intervention.     

Brain injury in the infant: the old, the new, and the uncertain

Although neonatal brain injury occurs most frequently after a perinatal hypoxic-ischemic insult, recently studies have noted that variable causes such as metabolic and reperfusion events can result in, or aggravate, a brain insult. Current data suggest that about 2 to 5 of 1,000 live births in the United States and more so in developing countries experience a brain injury Approximately 20% to 40% of infants who survive the brain injury develop significant neurological and developmental impairments. The resulting impact on the child, family, and society presents a formidable challenge to health care professionals. Although several important insights have been gained in the last several years about the epidemiology, diagnosis, and mechanism of brain injury, management remains mostly a cocktail of controversial trials. This article provides a comprehensive review of the pathology, clinical manifestations, and timely management of infants with brain injury.     

高压氧对脑外伤后一氧化氮及脑水肿的影响

观察高压氧对脑外伤后脑水肿及一氧化氮的影响。方法：建立大鼠液压脑外伤模型，采用生化、放免等方法观察脑外伤后不同时期高压氧（ＨＢＯ）治疗组和未治疗组血浆一氧化氮（ＮＯ）、脑组织ＮＯ、环磷酸鸟苷酸（ｃＧＭＰ）及脑组织含水量的变化，并进行病理学检查。结果：ＨＢＯ治疗组血浆ＮＯ、脑组织含水量、腋组织ＮＯ及ｃＧＭＰ较未治疗组均有不同程度下降（Ｐ＜０．０５）。脑组织含水量与血浆ＮＯ及脑组织ＮＯ、ｃＧＭＰ之间呈正相关关系（ｒ＝０．３４１４、０．３８１９、０．４８０４、Ｐ＜０．０５），病理检查可见ＨＢＯ治疗组脑组织损伤较轻。结论：ＨＢＯ能减轻脑外伤后脑水肿，并抑制脑外伤后ＮＯ的过量生成。ＨＢＯ减轻脑外伤后脑水肿的机制与ＮＯ有关。     

No long-term benefit from hypothermia after severe traumatic brain injury with secondary insult in rats

OBJECTIVES: To evaluate the effect of application of transient, moderate hypothermia on outcome after experimental traumatic brain injury (TBI) with a secondary hypoxemic insult. DESIGN: Prospective, randomized study. SETTING: University-based animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: All rats were subjected to severe TBI followed by 30 mins of moderate hypoxemia, associated with mild hypotension. Rats were randomized to three groups: a) normothermia (37 degrees C + 0.5 degrees C); b) immediate hypothermia (32 degrees C +/- 0.5 degrees C initiated after trauma, before hypoxemia); and c) delayed hypothermia (32 degrees C +/- 0.5 degrees C after hypoxemia). The brain temperature was controlled for 4 hrs after TBI and hypoxemia. MEASUREMENTS AND MAIN RESULTS: Animals were evaluated after TBI for motor and cognitive performance using beam balance (days 1-5 after TBI), beam walking (days 1-5 after TBI), and Morris Water Maze (days 14-18 after TBI) assessments. On day 21 after TBI, rats were perfused with paraformaldehyde and brains were histologically evaluated for lesion volume and hippocampal neuron counts. All three groups showed marked deficits in beam balance, beam walking, and Morris Water Maze performance. However, these deficits did not differ between groups. There was no difference in lesion volume between groups. All animals had significant hippocampal neuronal loss on the side ipsilateral to injury, but this loss was similar between groups. CONCLUSIONS: In this rat model of severe TBI with secondary insult, moderate hypothermia for 4 hrs posttrauma failed to improve motor function, cognitive function, lesion volume or hippocampal neuronal survival. Combination therapies may be necessary in this difficult setting.     

骨髓间充质干细胞治疗新生鼠缺氧缺血性脑损伤的研究

目的观察骨髓间充质干细胞移植治疗新生鼠缺氧缺血性脑损伤对小胶质细胞和神经元表达的影响。方法将10日龄C57BL/6小鼠60只按随机区组法分为假手术组、缺氧缺血组、安慰剂组和干细胞组, 每组15只小鼠。缺氧缺血组、安慰剂组和干细胞组均进行缺氧缺血模型制备, 假手术组仅颈部切口后缝合。安慰剂组造模完成后用脑立体定位仪下在前囟点注射磷酸盐缓冲液, 干细胞组造模完成后用同样的方法在同一位置注射骨髓间充质干细胞。干细胞组移植7 d后, 取4组小鼠的脑组织, 用透射电镜观察其脑组织超微结构, 采用免疫荧光染色观察4组小鼠左侧脑皮质神经元和小胶质细胞表达情况, 并进行比较。结果干细胞移植7 d后, 干细胞组神经元形态改善, 神经纤维肿胀减轻。干细胞移植7 d后, 皮质区神经元的表达存在组间差异[F(3, 8)=88.080, P<0.05], 干细胞组小鼠左侧皮质神经元表达显著多于缺氧缺血组和安慰剂组, 差异均有统计学意义(P<0.05);干细胞移植7 d后, 皮质区小胶质细胞的表达存在组间差异[F(3, 8)=11.331, P=0.003], 干细胞组小胶质细胞的表达显著低于缺氧缺血...     

Therapeutics for neonatal brain injury

Neonatal brain injury is an important cause of death and neurodevelopmental delay. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead to both early and late phases of cell damage and death. Therapies targeting these different pathways have shown potential in protecting the brain from ongoing injury. More recent therapies, such as growth factors, have demonstrated an ability to increase cell proliferation and repair over longer periods of time. Even though hypothermia, which decreases cerebral metabolism and possibly affects other mechanisms, may show some benefit in particular cases, no widely effective therapeutic interventions for human neonates exist. In this review, we summarize recent findings in neuroprotection and neurogenesis for the immature brain, including combination therapy to optimize repair.     

亚低温对大鼠局灶性脑缺血氧自由基和一氧化氮的影响

目的研究亚低温状态下,大鼠急性脑缺血时氧自由基—超氧化物歧化酶（SOD）和一氧化氮（NO）、一氧化氮合酶（NOS）的改变,探讨亚低温对缺血脑组织的保护机制。方法将45只Wistar大鼠随机分为9组,假手术组5只,缺血组及亚低温组又根据缺血、亚低温时间不同分为：3 h2、4 h4、8 h7、2 h亚组（各组均为5只）。采用颈内动脉线栓法制备大鼠大脑中动脉闭塞（MCAO）模型。结果比较缺血组和亚低温组,可见亚低温组栓塞侧脑组织超氧化物歧化酶（SOD）的生成和释放明显增加;亚低温组血清中一氧化氮（NO）、一氧化氮合酶（NOS）的生成和释放明显减少。结论亚低温状态下、氧自由基系统及一氧化氮（NO）、一氧化氮合酶（NOS）的改变,是其保护缺血神经元的重要机制。     

Cardiac arrest caused by accidental severe hypothermia and myocardial infarction during general anesthesia

Therapeutic hypothermia is often used for traumatic brain injury because of its neuroprotective effect and decreased secondary brain injury. However, this procedure lacks clinical evidence supporting its efficacy, and adverse outcomes have been reported during general anesthesia. A 61-year-old man with a history of percutaneous coronary intervention (PCI) was admitted with traumatic brain injury. Immediately after admission, he underwent mild therapeutic hypothermia with a target temperature of 33.0°C for neuroprotection. During general anesthesia for emergency surgery because he developed a mass effect, hypothermic cardiac arrest occurred following an additional decrease in the core body temperature. Moreover, myocardial infarction caused by restenosis of the previous PCI lesion also contributed to the cardiac arrest. Although the patient recovered spontaneous circulation after an hour-long cardiopulmonary resuscitation with rewarming, he eventually died of subsequent repetitive cardiac arrests. When anesthetizing patients undergoing therapeutic hypothermia, caution is required to prevent adverse outcomes that can be caused by unintentional severe hypothermia and exacerbation of underlying heart disease.     

黄芪对急性脑损伤后一氧化氮合酶活性的抑制作用

背景黄芪在机体免疫功能调节中具有重要作用,而在对急性颅脑损伤干预中是否具有神经元保护作用,且其发挥作用的途径何在?目的观察黄芪对脑损伤后脑组织一氧化氮合酶活性的影响.设计随机对照的实验.单位兰州军区神经外科研究所.对象实验于2001-09/12在兰州军区神经外科研究所实验室完成.取健康雄性SD大鼠54只,随机分为3组脑损伤组(n=24),黄芪组(n=24),对照组(n=6),损伤组与黄芪组均分为伤后0.5,2,6和24 h4个时间点,每个时间点6只动物.方法脑损伤组和黄芪组制备脑损伤模型,对照组仅开骨窗,不致伤.黄芪组致伤后立即腹腔注射黄芪200 mg/kg,用化学定量法检测大鼠脑损伤后不同时间点脑组织中一氧化氮合酶的活性.主要观察指标各组大鼠脑组织中一氧化氮合酶活性.结果54只大鼠全部进入结果分析.脑损伤组、黄芪组大鼠在伤后0.5 h一氧化氮合酶活性较对照组升高[46.44±13.45)(43.15±12.43),(40.46±12 85)nkat/L,P＜0.05],伤后2 h达高峰[(67.49±22.45),(64.26±19.78)nkat/L,P＜0.01],伤后6 h开始下降[(63.46±24.68),(52.91±21.36)nkat/L,P＜0.01],伤后24 h降至基础水平[(41.23±12.57),(40.92±12.25)nkat/L,P＞0.05].黄芪组在伤后2,6 h一氧化氮合酶活性较损伤组明显降低(P＜0.01,0.05).结论颅脑损伤后,受损脑组织中一氧化氮合酶活性呈节段性升高,黄芪可通过抑制损伤后脑组织中一氧化氮合酶活性,起到保护创伤神经元的作用.     

Moderate brain hypothermia started before resuscitation improves survival and neurobehavioral outcomes after CA/CPR in mice

Aim of the studyNo definitive experimental or clinical evidence exists whether brain hypothermia before, rather than during or after, resuscitation can reduce hypoxic-ischemic brain injury following cardiac arrest/cardiopulmonary resuscitation (CA/CPR) and improve outcomes. We examined the effects of moderate brain hypothermia before resuscitation on survival and histopathological and neurobehavioral outcomes in a mouse model.MethodsAdult C57BL/6 male mice (age: 8–12 weeks) were subjected to 8-min CA followed by CPR. The animals were randomly divided into sham, normothermia (NT; brain temperature 37.5 °C), and extracranial hypothermia (HT; brain temperature 28–32 °C) groups. The hippocampal CA1 was assessed 7 day after resuscitation by histochemical staining. Neurobehavioral outcomes were evaluated by the Barnes maze (BMT), openfield (OFT), rotarod, and light/dark (LDT) tests. Cleaved caspase-3 and heat shock protein 60 (HSP70) levels were investigated by western blotting.ResultsThe HT group exhibited higher survival and lower CA1 neuronal injury than did the NT group. HT mice showed improved spatial memory in the BMT compared with NT mice. NT mice travelled a shorter distance in the OFT and tended to spend more time in the light compartment in the LDT than did sham and HT mice. The levels of cleaved caspase-3 and HSP70 were non-significantly higher in the NT than in the sham and HT groups.ConclusionsModerate brain hypothermia before resuscitation improved survival and reduced histological neuronal injury, spatial memory impairment, and anxiety-like behaviours after CA/CPR in mice.     

Moderate hypothermia may be detrimental after traumatic brain injury in fentanyl-anesthetized rats

OBJECTIVES: To determine whether transient, moderate hypothermia is beneficial after traumatic brain injury in fentanyl-anesthetized rats. DESIGN: Prospective, randomized study. SETTING: University-based animal research facility. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: All rats were intubated, mechanically ventilated, and anesthetized with fentanyl (10 microg/kg intravenous bolus and then 50 microg.kg(-1).hr(-1) infusion). Controlled cortical impact was performed to the left parietal cortex, followed immediately by 1 hr of either normothermia (brain temperature 37 +/- 0.5 degrees C) or hypothermia (brain temperature 32 +/- 0.5 degrees C). Hypothermic rats were rewarmed gradually over 1 hr. Fentanyl anesthesia and mechanical ventilation were continued in both groups until the end of rewarming (2 hrs after traumatic brain injury). MEASUREMENTS AND MAIN RESULTS: Histologic assessment performed 72 hrs after traumatic brain injury was the primary outcome variable. Secondary outcome variables were physiologic variables monitored during the first 2 hrs after traumatic brain injury and plasma catecholamine and serum fentanyl concentrations measured at the end of both hypothermia and rewarming (1 and 2 hrs after traumatic brain injury). Contusion volume was larger in hypothermic vs. normothermic rats (44.3 +/- 4.2 vs. 28.6 +/- 4.0 mm, p <.05), but hippocampal neuronal survival did not differ between groups. Physiologic variables did not differ between groups. Plasma dopamine and norepinephrine concentrations were increased at the end of hypothermia in hypothermic (vs. normothermic) rats (p <.05), indicating that hypothermia augmented the systemic stress response. Similarly, serum fentanyl concentrations were higher in hypothermic (vs. normothermic) rats at the end of both hypothermia and rewarming (p <.05), demonstrating that hypothermia reduced the clearance and/or metabolism of fentanyl. CONCLUSIONS: Moderate hypothermia was detrimental after experimental traumatic brain injury in fentanyl-anesthetized rats. Since treatment with hypothermia has provided reliable benefit in experimental traumatic brain injury with inhalational anesthetics, these results indicate that the choice of anesthesia/analgesia after traumatic brain injury may dramatically influence response to other therapeutic interventions, such as hypothermia. Given that narcotics commonly are administered to patients after severe traumatic brain injury, this study may have clinical implications.     

亚低温辅助运动通过抑制脑神经凋亡改善缺氧缺血性脑损伤大鼠幼崽脑神经功能的机制探讨

目的探讨亚低温辅助运动通过抑制脑神经凋亡改善缺氧缺血性脑损伤大鼠幼崽脑神经功能的机制。方法选择无特定病原体(SPF)级新生7日龄Wistar大鼠,采用手术结扎左颈总动脉法建立缺氧缺血性脑损伤幼鼠模型。按照随机数字表法分为假手术组(假手术幼鼠,正常饲养不进行任何干预)、HIE模型组(HIE模型幼鼠,正常饲养不进行任何干预)和HIE模型+亚低温和运动干预组(HIE模型幼鼠,亚低温和运动干预),每组大鼠幼崽各5只,共干预63 d。分别于治疗前以及治疗后第42天和第63天,通过旋转脚架性能测试检测3组幼鼠平衡能力变化、去除胶带测试检测3组幼鼠行为能力变化;治疗结束后,采用蛋白质印迹(Western blotting)法检测治疗前后模型幼鼠的脑部凋亡相关蛋白因子细胞色素c(Cyt C)、活化型半胱天冬酶-3(cleaved-Caspase 3)、半胱天冬酶-3前体(pro-Caspase 3)、聚ADP核糖聚合酶1(PARP-1)、蛋白酶激活受体(PAR)的表达情况。结果第42天和第63天,与假手术组相比,HIE模型组和HIE模型+亚低温和运动干预组幼鼠平衡维持时间均显著缩短,去除胶带所用时间、海马组织中凋亡相关蛋白Cyt C、cleaved-Caspase 3、PARP-1和PAR相对表达量均显著增加,差异均有统计学意义(P<0.05)。与HIE模型组相比,HIE模型+亚低温和运动干预组幼鼠平衡维持时间均显著延长,去除胶带所用时间、海马组织中凋亡相关蛋白Cyt C、cleaved-Caspase 3、PARP-1和PAR相对表达量均显著降低,差异均有统计学意义(P<0.05)。结论亚低温辅助运动治疗能够显著改善缺氧缺血性脑损伤大鼠幼崽的行为能力,其作用机制可能与调控幼鼠海马组织凋亡蛋白及PARP-1、PAR的表达有关,其治疗效果虽较为显著但要达到完全康复,仍存在疗效差距。     

Novel applications of therapeutic hypothermia: report of three cases

Therapeutic hypothermia can provide neuroprotection in various situations where global or focal neurological injury has occurred. Hypothermia has been shown to be effective in a large number of animal experiments. In clinical trials, hypothermia has been used in patients with postanoxic injury following cardiopulmonary resuscitation, in traumatic brain injury with high intracranial pressure, in the perioperative setting during various surgical procedures and for various other indications. There is thus evidence that hypothermia can be effective in various situations of neurological injury, although a number of questions remain unanswered. We describe three patients with unusual causes of neurological injury, whose clinical situation was in fundamental aspects analogous to conditions where hypothermia has been shown to be effective.     

新生猪缺氧缺血脑损伤后基底节乳酸代谢及其转运体表达的研究

目的通过~1H-MRS在体检测新生猪缺氧缺血脑损伤(HIBI)模型在损伤后不同时间点乳酸含量的变化并与乳酸转运体(MCT-2、MCT-4)的表达特征进行相关研究,以期进一步明确乳酸在HI后脑损伤中的作用机制。材料与方法选用出生后3~5 d的健康新生猪,体重约为1~1.5 kg,对照组5头,HIBI模型组30头。通过1H-MRS成像检测缺氧缺血后不同时间点基底节区乳酸的变化并与MCT-2、MCT-4的表达进行相关分析,P0.05认为差异有统计学意义。结果 (1)~1H-MRS结果显示,HIBI后Lac峰值出现在2~6 h,随后Lac逐渐下降,逐步降低至与对照组水平相当。除24~48 h、48~72 h与对照组差异无统计学意义(P=0.86、0.26)外,其余模型组与对照组差异均有统计学意义(P0.05)。(2)MCT-2、MCT-4在HI后表达先上调后降低,均在12~24 h达到高峰,与其余组均有统计学差异(P0.05)。结论缺氧缺血后,乳酸含量的变化可调节神经元及胶质细胞乳酸相关转运体的表达。     

The effect of hypothermia and hyperthermia on acute brain injury

The brain is extraordinarily susceptible to changes in temperature. Hyperthermia has been shown to exacerbate the biochemical cascade of secondary brain injury. Inversely, hypothermia limits the damaging effects of secondary brain injury. There has been a great deal of investigation regarding the detrimental effects of hyperthermia and the neuroprotection of hypothermia in animal studies. Within the last decade, clinical trials have begun to establish how the brain reacts to both temperature extremes. In the future, studies of hypothermia will continue in the quest of the optimal timing and degree of hypothermia. Hyperthermia will be examined in depth for its detrimental effects on an injured brain. Interventions for the prevention and treatment of hyperthermia will be explored. Nurses will implement cooling strategies to induce hypothermia, applying interventions to prevent complications, and they will also diagnose hyperthermia, deciding when and if to intervene pharmacologically and therapeutically. These advanced nursing actions will be guided by knowledge and understanding of available evidence. This article presents the pathophysiology of secondary brain injury and how it is affected by both hypothermia and hyperthermia. A review of the research leading up to clinical trials is explored, as well as a discussion of the future of temperature modulation for the brain injury patient. This information will help healthcare providers understand the effect that both hypothermia and hyperthermia have on the acutely injured brain.     

Induced hypothermia in critical care medicine: a review

BACKGROUND: Clinical trials of induced hypothermia have suggested that this treatment may be beneficial in selected patients with neurologic injury. OBJECTIVES: To review the topic of induced hypothermia as a treatment of patients with neurologic and other disorders. DESIGN: Review article. INTERVENTIONS: None. MAIN RESULTS: Improved outcome was demonstrated in two prospective, randomized, controlled trials in which induced hypothermia (33 degrees C for 12-24 hrs) was used in patients with anoxic brain injury following resuscitation from prehospital cardiac arrest. In addition, prospective, randomized, controlled trials have been conducted in patients with severe head injury, with variable results. There also have been preliminary clinical studies of induced hypothermia in patients with severe stroke, newborn hypoxic-ischemic encephalopathy, neurologic infection, and hepatic encephalopathy, with promising results. Finally, animal models have suggested that hypothermia that is induced rapidly following traumatic cardiac arrest provides significant neurologic protection and improved survival. CONCLUSIONS: Induced hypothermia has a role in selected patients in the intensive care unit. Critical care physicians should be familiar with the physiologic effects, current indications, techniques, and complications of induced hyperthermia.