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INVITED REVIEW J Neurocrit Care 2009;2 Suppl 2:S62-S67 ISSN 2005-0348 저체온요법 서울대학교의과대학분당서울대학교병원뇌졸중센터, 신경과학교실 한문구 Therapeutic Hypothermia Moon-Ku Han, MD Department of Neurology, Stroke Center, Seoul

1 INVITED REVIEW J Neurocrit Care 2009;2 Suppl 2:S62-S67 ISSN 저체온요법 서울대학교의과대학분당서울대학교병원뇌졸중센터, 신경과학교실 한문구 Therapeutic Hypothermia Moon-Ku Han, MD Department of Neurology, Stroke Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea Background: Hypothermia is being used with increasing frequency to prevent or mitigate various types of neurologic injury. In addition, symptomatic fever control is becoming an increasingly accepted goal of therapy in patients with neurocritical illness. However, effectively controlling fever and inducing hypothermia poses special challenges to the intensive care unit team and others involved in the care of critically ill patients. Objective: To discuss practical aspects and pitfalls of therapeutic temperature management in critically ill patients. Results: Cooling can be divided into three distinct phases: induction, maintenance, and rewarming. Each has its own risks and management problems. A number of cooling devices that have reached the market in recent years enable reliable maintenance and slow and controlled rewarming. Rapid induction decreases the risks and consequences of short-term side effects, such as shivering and metabolic disorders. Cardiovascular effects include bradycardia and a rise in blood pressure. Hypothermia's effect on myocardial contractility is variable (depending on heart rate and filling pressure); in most patients myocardial contractility will increase, although mild diastolic dysfunction can develop in some patients. A risk of clinically significant arrhythmias occurs only if core temperature decreases below 30. The most important long-term side effects of hypothermia are infections (usually of the respiratory tract or wounds) and bedsores. Conclusion: Temperature management and hypothermia induction are gaining importance in critical care medicine. Intensive care unit physicians, critical care nurses, and others (emergency physicians, neurologists, and cardiologists) should be familiar with the physiologic effects, current indications, techniques, complications and practical issues of temperature management, and induced hypothermia. In experienced hands the technique is safe and highly effective. J Neurocrit Care 2009;2 Suppl 2:S62-S67 KEY WORDS: Hypothermia Therapeutic Definitions Fever control Normothermia Side effects Neurologic injury Cardiac arrest Traumatic brain injury. 서 론 TABLE 1. Proposed terms and definitions surrounding therapeutic hypothermia 치료적인저체온 (therapeutic hypothermia) 유도요법은환자의심부체온 (core temperature) 을 32~35 로적극적으로낮추는것으로정의되며, 현재다양한신경손상을예방하거나줄이는방법으로서치료빈도가급격히증가하는치료방법이다 (Table 1). 최근에 ischemia 또는 trauma 후수분또는수시간안에 Address for correspondence: Moon-Ku Han, MD Department of Neurology, Stroke Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 166 Gumi-ro, Bundang-gu, Seongnam , Korea Tel: , Fax: mkhan@snu.ac.kr S62 Copyright c 2009 The Korean Neurocritical Care Society

2 Therapeutic Hypothermia MK Han TABLE 2. Currently available methods and devices for inducing and maintaining hypothermia S63

3 J Neurocrit Care 2009;2 Suppl 2:S62-S67 TABLE 2. Continued 손상된뇌를더파괴하는과정에대한이해가증가하였다. 이러한과정을, 무산소손상 (post-anoxic injury) 후 postresuscitation disease와 reperfusion injury라고하며, 외상성손상 (traumatic brain injury) 의경우에서는 secondary brain injury 라고한다. 이과정은초기손상후에수시간에서수일에걸쳐서지속되며, 새로운허혈손상 (ischemic injury) 에의해다시촉진되기도한다. 가장중요한것은이모든과정이온도의존성 (temperature dependent) 이라는것이며, 이과정들이열에의해서자극또는촉발될수있고 mild 또는 moderate hypothermia 에의해서완화또는차단할수있다. 저체온의이러기전에따른폭넓은효과가치료적인저체온유도가왜임상적으로효과적인지를증명할수있으며, 이차적인뇌손상과정중한부분에만작용하는약물투약의효과가성공적이지못한지를설명할수있다. 1 본문 American Heart Association과 European Resuscitation Council 의가장최근치료가이드에서는치료적저체온유도요법을심정지 (cardiac arrest) 후혼수상태로있는선택된환자들에서사용하도록권고하고있다. 2 그밖에도여러가지의상황들, 심각한외상성뇌손상 (severe traumatic brain injury), 뇌졸중 (stroke), 간부전 (hepatic failure), 척수손상 (spinal cord injury), 심근경색 (myocardial infarction), 고위험환자의수술에서치료적저체온유도요법을사용할수있다. 1-5 저체온유도요법이임상적으로가장넓게적용되는경우는심장정지후에발생한넓은허혈뇌손상의치료이다. 병원밖에서심정지후다시혈류가다시회복되었을때의식이혼수상태인경우에가장폭넓게사용되고있다. 저체온 S64

Therapeutic Hypothermia MK Han 요법에서는초기 8시간안에 32 를유도하여 12시간에서 24시간까지유지를하며, 시간당 0.2 의속도록다시체온을정상화시킨다. 6 전신저체온요법에대한연구들은대부분 external cooling 방법을사용하였고최근에는 endovascular device을이용한저체온요법이증가하고있다 (Table 2).

4 Therapeutic Hypothermia MK Han 요법에서는초기 8시간안에 32 를유도하여 12시간에서 24시간까지유지를하며, 시간당 0.2 의속도록다시체온을정상화시킨다. 6 전신저체온요법에대한연구들은대부분 external cooling 방법을사용하였고최근에는 endovascular device을이용한저체온요법이증가하고있다 (Table 2). 저체온을유도하기위해서물수환 (water circulating) 또는공기순환 (air circulating) 냉각담요 (cooling blanket), surface ice packs, iced gastric lavage 등이사용된다. 물순환냉각담요가가장효과적이고빠른방법이다. 최근에는효과적인한층발전된 external cooling 과 endovascular cooling이더빠른효과를나타내고있다. 현재저체온요법에서목표체온은 32~34 이다. 심부체온을측정하는법으로는대부분방광안에체온을이용하고있으나최근에는식도내체온을측정하는방법도사용되고있다. 심정지후뇌손상으로인한혼수환자에게저체온요법은 12~24 시 TABLE 3. The most important physiological changes and potential side effects of hypothermia S65

5 J Neurocrit Care 2009;2 Suppl 2:S62-S67 간사용하며, 뇌졸중에대해서는아직불확실하다. 저체온요법의부작용으로는감염의증가, 특히폐렴의발생이발생한다. 그래서저체온요법을받는모든환자는감염에대하여항상모니터링야한다 (Table 3). 7 두번째로많이발생하는부작용은응고병증 (coagulopathy) 이다. 응고병증은저체온자체에의한효과에의한것이다. Cooling phase 에서혈액내전해질 (electrolyte), K, Mg, Ca, P 등이빠르게떨어질수있다. 또다른부작용중의하나가 shivering이다 (Table 4). Shivering을막기위해서신경근차 단제를사용하기도하지만, 신경근차단제에의한마비가발생할수도있다. Shivering 을막기위한다른방법으로서 buspirone 30 mg을구강복용하고 meperidine을주사로투여하여 shivering 역치를 33.4 로, 2.3 낯출수있다. 결론 저체온유도요법은심정지후혼수환자뿐아니라, 외상성뇌손상환자등현재폭넓게사용되고있으며, 심정지초 TABLE 4. Drugs that can be used to control shivering S66

Therapeutic Hypothermia MK Han TABLE 5. Practical checklist of issues to address and to avoid durine management 기상태, 뇌경색, 지주막하출혈, 심도자중저체온요법등으로적용영역이넓어지고있다. 저체온유도는뇌뿐만아니라, 신체내의모든장기에수많은생리적인변화를일으킨다.

6 Therapeutic Hypothermia MK Han TABLE 5. Practical checklist of issues to address and to avoid durine management 기상태, 뇌경색, 지주막하출혈, 심도자중저체온요법등으로적용영역이넓어지고있다. 저체온유도는뇌뿐만아니라, 신체내의모든장기에수많은생리적인변화를일으킨다. 중환자집중치료실에서저체온요법을적용하는의사와간호사는저체온과연관된여러가지생리적인변화와병태생리학적인변화, 그리고각종부작용에대하여인지하 고저체온요법을능숙하게할수있도록훈련이되어있어야한다 (Table 5). 저체온치료의성공여부는여러가지부작용을효과적으로예방하고치료함으로서가능하다. 또한 cooling과 rewarming에대한자세한치료 protocol 이저체온치료성공의중요한요소이다. 이런한모든것들이조화를이루어적용될때효과적으로치료를할수있으며, 저체온요법을더많은질환에사용할수있을것이다. REFERENCES 1. Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet 2008;371: Nolan JP, Deakin CD, Soar J, et al. European Resuscitation Council guidelines for resuscitation Section 4. Adult advanced life support. Resuscitation 2005;67(Suppl 1):S Polderman KH. Application of therapeutic hypothermia in the ICU: opportunities and pitfalls of a promising treatment modality, Part 1. Indications and evidence. Intensive Care Med 2004;30: Bernard SA, Buist M. Induced hypothermia in critical care medicine: a review. Crit Care Med 2003;31: Leslie K, Sessler DI. Perioperative hypothermia in the high-risk surgical patient. Best Pract Res Clin Anaesthesiol 2003;17: Polderman KH. Application of therapeutic hypothermia in the intensive care unit. Opportunities and pitfalls of a promising treatment modality, Part 2. Practical aspects and side effects. Intensive Care Med 2004;30: Tortorici MA, Kochanek PM, Poloyac SM. Effects of hypothermia on drug disposition, metabolism, and response: a focus of hypothermiamediated alterations on the cytochrome P450 enzyme system (review). Crit Care Med 2007;35: S67

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract