14-이병국

대한응급의학회지제 25 권제 6 호 Volume 25, Number 6, December, 2014 원 저 Resuscitation 우리나라에서병원전심정지후저체온치료의결과와현황 - 한국저체온치료연구회환자등록체계를이용하여 - 이차게재 전남대학교의과대학응급의학교실, 가톨릭대학교의학전문대학원응급의학교실 1, 한림대학교의과대학강남성심병원응급의학과 2, 인제대학교일산백병원응급의학과 3, 아주대학교병원응급의학과 4, 서울아산병원응급의학과 5, 충북대학교의과대학응급의학교실 6, 연세대학교의과대학응급의학교실 7, 경북대학교의과대학응급의학교실 8, 서울대학교의과대학응급의학교실 9, 한림의대성심병원응급의학과 10, 서울특별시시립보라매병원응급의학과 11, 충남대학교의과대학응급의학교실 12, 중앙대학교의과대학응급의학교실 13, 경희대학교의학전문대학원응급의학교실 14, 순천향대학교부천병원응급의학교실 15, 대구가톨릭대학교의과대학응급의학교실 16, 한림대학교의과대학강동성심병원응급의학과 17, 한전의료재단한일병원응급의학과 18, 연세대학교원주의과대학응급의학교실 19, 울산대학교의과대학응급의학교실 20, 이화여자대학교의과대학응급의학교실 21 이병국 박규남 1 강구현 2 김경환 3 김기운 4 김원영 5 민진홍 6 박유석 7 박정배 8 서길준 9 손유동 10 신종환 11 오주석 1 유연호 12 이동훈 13 이종석 14 임 @ 훈 15 장태창 16 조규종 17 조인수 18 차경철 19 최승필 1 최욱진 20 한 @ 철 21 한국저체온치료연구회 Outcome and Current Status of Therapeutic Hypothermia Following Out-of-hospital Cardiac Arrest in Korea from the Korea Hypothermia Network Registry Byung Kook Lee, M.D., Kyu Nam Park, M.D. 1, Gu Hyun Kang, M.D. 2, Kyung Hwan Kim, M.D. 3, Giwoon Kim, M.D. 4, Won Young Kim, M.D. 5, Jin Hong Min, M.D. 6, Yooseok Park, M.D. 7, Jung Bae Park, M.D. 8, Gil Joon Suh, M.D. 9, Yoo Dong Son, M.D. 10, Jonghwan Shin, M.D. 11, Joo Suk Oh, M.D. 1, Yeon Ho You, M.D. 12, Dong Hoon Lee, M.D. 13, Jong Seok Lee, M.D. 14, Hoon Lim, M.D. 15, Tae Chang Jang, M.D. 16, Gyu Chong Cho, M.D. 17, In Soo Cho, M.D. 18, Kyoung Chul Cha, M.D. 19, Seung Pill Choi, M.D. 1, Wook Jin Choi, M.D. 20, Chul Han, M.D. 21, Korea Hypothermia Network Purpose: Therapeutic hypothermia (TH) has become a standard strategy for reducing brain damage in the postresuscitation period. The aim of this study is to investigate the outcomes and current performance of TH with out-ofhospital cardiac arrest (OHCA) survivors through the Korean hypothermia network (KORHN) registry. 책임저자 : 박규남서울특별시서초구반포대로 22 가톨릭대학교의학전문대학원응급의학교실 Tel: 02) 2258-6302, Fax: 02) 2258-1997 E-mail: emsky@catholic.ac.kr 접수일 : 2014년 1월 18일, 1차교정일 : 2014년 1월 21일게재승인일 : 2014년 3월 31일 이논문은 Clin Exp Emerg Med 2004 Vol(1) No(1) 에보고된연구에기초한것임. 747 Methods: We used the KORHN registry, a web-based, multicenter registry that includes 24 participating hospitals throughout the Republic of Korea. Adult comatose OHCA survivors treated with TH from 2007 to 2012 were included. The primary outcomes were neurologic outcome at hospital discharge and in-hospital mortality. The secondary outcomes were TH performance and adverse events during TH. Results: A total of 930 patients were included; of these, 556 (59.8%) patients survived to discharge and 249 (26.8%) were discharged with good neurologic outcomes. The median time from return of spontaneous circulation (ROSC) to the start of TH was 101 (interquartile range (IQR): 46-200) minutes. The induction, maintenance, and rewarming durations were 150 (IQR: 80-267) minutes, 1440 (IQR: 1290-1440) minutes, and 708 (IQR: 420-900) minutes, respectively. The time from the ROSC to coronary angiography was 1,045 (IQR: 121-12,051) hours. Hyperglycemia (46.3%) was the most frequent adverse event. Conclusion: Over one quarter of OHCA survivors (26.8%) were discharged with good neurologic outcome. TH performance was managed appropriately in terms of the factors related to the timing of TH, which were the start time for cooling and the rewarming duration. Key Words: Out-of-hospital cardiac arrest, Induced hypothermia, Registries Department of Emergency Medicine, School of Medicine, Chonnam National University, Gwangju, Korea, Department of Emergency Medicine, School of Medicine, The Catholic University of Korea, Seoul, Korea 1, Department of Emergency Medicine, Kangnam Sacred Heart Hospital, Hallym University, Seoul, Korea 2, Department of Emergency Medicine, Inje

748 / 대한응급의학회지 : 제 25 권제 6 호 2014 University Ilsan Paik Hospital, Goyang, Korea 3, Department of Emergency Medicine, Ajou University Hospital, Suwon, Korea 4, Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea 5, Department of Emergency Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea 6, Department of Emergency Medicine, College of Medicine, Yonsei University, Seoul, Korea 7, Department of Emergency Medicine, School of Medicine, Kyungpook National University, Daegu, Korea 8, Department of Emergency Medicine, College of Medicine, Seoul National University, Seoul, Korea 9, Department of Emergency Medicine, College of Medicine, Hallym University, Anyang, Korea 10, Department of Emergency Medicine, Seoul National University Boramae Medical Center, Seoul, Korea 11, Department of Emergency Medicine, College of Medicine, Chungnam National University, Daejeon, Korea 12, Department of Emergency Medicine, College of Medicine, Chung-Ang University, Seoul, Korea 13, Department of Emergency Medicine, School of Medicine, Kyung Hee University, Seoul, Korea 14, Department of Emergency Medicine, College of Medicine, Soonchunhyang University, Gyeonggi-do, Korea 15, Department of Emergency Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea 16, Department of Emergency Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University Medical Center, Seoul, Korea 17, Department of Emergency Medicine, Hanil General Hospital, Korea Electric Power Medical Corporation, Seoul, Korea 18, Department of Emergency Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea 19, Department of Emergency Medicine, College of Medicine, Ulsan University, Ulsan, Korea 20, Department of Emergency Medicine, Ewha Womans University, Shool of Medicine, Seoul, Korea 21 Article Summary 서론많은심정지환자들은자발순환이회복되더라도의식을회복하지못하거나사망하게된다 1). 저체온치료는심정지이후에진행하는사립체손상, 세포막손상, 세포내산성화, 활성산소의형성, 흥분독성의증가등의허혈-재관류손상을감쇠시켜서신경손상을감소시킨다 2-5). 미국심장협회 (American Heart Association, AHA) 는심실세동이나무맥성심실빈맥으로인한병원전심정지환자에게저체온치료 ( 목표체온, 32~34 C; 유지기간 12~24시간 ) 를 Class I으로권장하고있으며, 제세동이필요하지않은리듬이나병원내심정지환자에게도 Class IIb로권장하고있다 6). 그러나, 위와같은가이드라인에도불구하고, 아직도저체온치료와관련하여서는그적용대상이나구체적방법등확립되지않은영역이많이있다. 예를들어, 병원전심정지뿐만아니라병원내심정지나, 제세동이필요하지않은심정지에대한효과는아직분명하지않고최적의목표체온이나유지기간에도이견이있다 7-12). 나라별로심정지의원인과초기심정지리듬의분포, 심정지에대처하는체계가다르며, 심정지후치료정책및예후또한다르다 13-17). 그러므로우리실정에맞는가이드라인을제시하기위해서는우리나라의현황을파악하여그근거를제시해야한다. 하지만, 우리나라에서저체온치료를받은심정지환자를대상으로한다기관등록체계의연구결과는아직까지발표된바가없다. 따라서본연구는현재우리나라의저체온치료를포함한심정지후치료의현황과치료결과를파악하고자한다. 대상과방법 1. 대상환자및등록체계 What is already known in the previous study The effectiveness of therapeutic hypothermia (TH) in cardiac arrest survivors has been proven. Several studies have reported on the outcome and status of post-cardiac arrest care including TH of their own countries. What is new in the current study Of 930 out-of-hospital cardiac arrest survivors treated with TH between 2007 and 2012, 59.8% survived to discharge and 26.8% were discharged with good neurological outcomes. This is the first report with large-scale multicentered registries in Korea. 병원전심정지환자의예후향상과저체온치료를포함한소생후치료의질적개선을위해서한국저체온치료연구회는웹을기반으로하는다기관환자등록체계를운영하였다. 2007년부터 2012년까지병원전심정지후자발순환은회복되었지만의식이회복되지않은 18세이상의성인들중저체온치료를받은환자들이등록체계에포함되었다. 18세미만의환자와외상으로인한심정지, 뇌졸중으로인한심정지, 병원내심정지는제외되었다. 등록체계에참가한 24 개기관의연구자 (investigator) 가환자의기본적인특성과기저질환, 병원전심정지정보, 자발순환회복후호흡과순환, 순환의보조방법, 신경학적상태와검사방법, 저체온치료실행관련정보, 합병증발생률, 퇴원시의최종임상결

이병국외 : 우리나라에서병원전심정지후저체온치료의결과와현황 - 한국저체온치료연구회환자등록체계를이용하여 - / 749 과를입력하였다. 3명의임상시험요원 (Clinical Research Associate, CRA) 이입력된정보를검토하였고, 최종적으로자료관리자 (Data Manager, DM) 가기관연구책임자에게되먹임하여정보입력을완료하였다. 2. 연구방법등록체계를통해다음과같은변수를추출하였다. 심정지발생연도, 연령, 성별, 과거병력 ( 관상동맥질환, 울혈성심부전, 뇌졸중, 고혈압, 당뇨, 폐질환, 신장질환, 간경변, 암 ), 심정지의목격여부, 목격자에의한심폐소생술시행여부, 초기심전도 ( 심실세동, 무맥성심실빈맥, 무수축, 무맥성전기활성, 알수없는경우 ), 심정지의원인 ( 심인성, 익수, 약물, 가사, 실혈, 기타비심인성 ), 자발순환회복이후재관류요법및순환보조방법 ( 관상동맥조영술, 관상동맥중재술, 관상동맥우회술, 체외순환보조, 대동맥내풍선펌프, 지속신대체요법 ), 관상동맥조영술시행까지의시간, 심정지로부터자발순환회복까지의시간, 자발순환회복후혈당, 자발순환회복후 Glasgow Coma Scale (GCS), 자발순환회복후저체온치료시작까지의시간, 저체온치료유도기간, 저체온치료유지기간, 저체온치료재가온기간, 목표체온, 쇽의여부, 저체온치료를위해이용한방법 ( 냉각담요, 얼음주머니, 냉각식염수정주, 냉각용혈관내카테터, 냉각수를이용한위와방광세척, 물수건, 선풍기, 부착형냉각패드, 냉각의류, 체외순환 ), 중심체온측정위치, 저체온치료시행중합병증의여부 ( 과냉각, 서맥, 저칼륨혈증, 고혈당, 출혈, 저혈압, 저체온치료후고체온증, 고칼륨혈증, 저혈당증, 발작, 폐렴, 패혈증 ), 퇴원시 Cerebral Performance Category scale (CPC), 퇴원시사망의여부를포함하였다. 초기심전도는 119 구급대혹은응급실에서측정한것중먼저측정한것으로정의하였다. 자발순환회복은순환이 20분이상유지되는경우로정의하였다. 심정지로부터자발순환회복까지의시간은심정지의목격시간혹은심정지의발견시간으로부터자발순환이회복된시간으로정의하였다. 과냉각은저체온치료중 32도미만, 고체온증은 38도이상, 서맥은분당 40회미만, 저칼륨혈증은 3.0 meq/l 이하, 고칼륨혈증은 5.0 meq/l 이상, 저혈당은 80 mg/dl 미만, 고혈당은 180 mg/dl이상, 저혈압은수축기혈압이 90 mmhg 미만혹은평균동맥압이 60 mmhg 미만으로 30분이상지속되거나, 이를유지하기위하여약물이나기기보조가필요한경우로정의하였다. 발작은임상적으로혹은뇌파검사에서확진된경우모두를포함하였다. 폐렴은흉부 X-선검사에서새로발생하거나진행하는병변, 발열, 백혈구증가, 화농성객담이배출되는경우로정의하였다. 3. 일차결과및이차결과일차결과는퇴원시신경학적예후와생존퇴원의여부이다. 퇴원시 CPC 점수를이용하였는데, CPC는점수에따라 CPC 1( 정상생활가능 ), CPC 2( 경도장애 ), CPC 3( 중증장애 ), CPC 4( 식물인간상태 ), CPC 5( 뇌사혹은사망 ) 로정의하였다 18). 신경학적예후는 CPC를기준으로 CPC 1, 2는예후우량군으로 CPC 3-5는예후불량군으로정의하였다. 이차결과는저체온치료의실행행태, 저체온치료관련합병증의발생이다. 4. 통계분석명목변수들은빈도 ( 백분율 ) 로표현하였고, 연속변수는정규성분포검정결과모두비정규분포를보였기때문에중앙값 ( 사분위값 ) 으로표현하였다. 비정규분포를보인연속변수의경향분석을위해서 Jonckheere-Terpstra 검정을이용하였다. 통계분석은 PASW/SPSSTM software, version 18 (IBM Inc., Chicago, USA) 를사용하였으며, p값이 0.05 미만인경우를통계학적으로유의하게판정하였다. 결과 1. 기관별환자의분포및일반적특성 24개기관에서등록된환자수는 930례였으며, 각증례의입력정보충실도의중앙값은 99.1% (98.1~100%) 였다. 기관당등록환자수의중앙값은 26 (11-51) 례였고, 최대환자수등록기관은 171례를, 최소환자수등록기관은 2례를등록하였다. 6개기관은 2007년이전부터저체온치료를시행하였고, 2개의기관은 2009년도부터, 6개기관은 2010년도부터, 9개기관은 2011년도부터시작하였으며, 2012년에이르러시작한기관이 1개였다. 참여한기관의지역적분포는 Fig. 1과같다. 연도별환자의분포는 2007년 39 (4.2%) 례, 2008년 49 (5.3%) 례, 2009년 75 (8.1%) 례, 2010년 117 (12.6%) 례, 2011년 274 (29.5%) 례, 2012년 375 (40.3%) 례로해마다증가하는추세를보였다. 대상환자의일반적인특징은 Table 1에기술하였다. 연령의중앙값은 58 (46-70) 세이다. 남성이 650 (69.9%) 례로여성보다많았으며, 기저질환으로는고혈압과당뇨의빈도가높았다. 심정지가목격된경우는 622 (66.9%) 례였으며, 목격자에의한심폐소생술은 281 (30.2%) 례였다. 심정지리듬은제세동이필요한리듬의경우가 243 (26.1%) 례, 제세동이필요치않은리듬이 653 (70.2%) 례로제세

750 / 대한응급의학회지 : 제 25 권제 6 호 2014 동이필요치않은리듬의빈도가높았다. 심정지의원인으로는심인성심정지가 564 (60.6%) 례로가장많았다. 2. 신경학적예후와생존율및심정지리듬에따른분석총 930례중 249 (26.8%) 례는퇴원시예후우량군이었으며, 556 (59.8%) 례는생존상태로퇴원하였다. 제세동이필요한리듬인 243례중 147 (60.5%) 례가예후우량군이었으며, 생존군은 202 (83.1%) 례였던반면에제세동이필요치않은리듬인 653례중 87 (13.3%) 례가예후우량군이었고, 생존군은 327 (50.1%) 례였다. 각리듬에따른신경학적예후와생존군의빈도는 Fig. 2와같다. 3. 저체온치료행태 ( 시간, 방법, 체온측정위치, 목표체온 ) 와합병증발생 Fig. 1. Geographic distribution of the 24 participating hospitals. 자발순환회복후저체온치료행태에관련된내용은 Table 2에제시하였다. 자발순환회복후저체온치료까지걸리는시간의중앙값은 101 (46-200) 분이었으며, 목표체온을 33 C 로설정하는경우가가장많았다. 목표체온까지도달하는시간의중앙값은 150 (80-267) 분이었으며, 재가온에걸린시간의중앙값은 708 (420-900) 분이었다. 연구기간동안시간이흐름에따라자발순환회복으로부터저체온치료시작까지의시간이감소하는경향을보였고 (p=0.002), 재가온기간이증가하는경향을보였다 (p< 0.001). (Table 3). 중심체온은직장에서측정하는경우 Fig. 2. Survival and neurologic outcome at discharge. Survival and neurologic outcome at discharge of the 930 out-of-hospital cardiac arrests treated with therapeutic hypothermia included in the study divided into initial rhythm of ventricular fibrillation/pulseless ventricular tachycardia, asystole, pulseless electrical activity, and unknown. Good neurologic outcome was defined as cerebral performance category 1 or 2. OHCA: out-of-hospital cardiac arrest, TH: therapeutic hypothermia, Vf: ventricular fibrillation, VT: ventricular tachycardia, PEA: pulseless electrical activity, CPC: cerebral performance category scale

이병국외 : 우리나라에서병원전심정지후저체온치료의결과와현황 - 한국저체온치료연구회환자등록체계를이용하여 - / 751 Table 1. Demographic data about patients and cardiac arrest events. n=930 Age (yr), median (IQR) 58 (46-70)0 Male geder, n (%) 650 (69.9) Comorbidity, n (%) Coronary heart disease 112 (12.0) Congestive heart failure 029 (03.1) Stroke 046 (04.9) Hypertension 321 (34.5) Diabetes mellitus 209 (22.5) Lung disease 056 (06.0) Renal impairment 058 (06.2) Liver cirrhosis 012 (01.3) Malignancy 027 (02.9) Witness, n (%) 622 (66.9) Bystander CPR, n (%) 281 (30.2) First monitored rhythm, n (%) Vf/pulseless VT 243 (26.1) Pulseless electrical activity 172 (18.5) Asystole 481 (51.7) Unknown 034 (03.7) Etiology of cardiac arrest, n (%) Cardiac 564 (60.6) Submersion 027 (02.9) Drug 027 (02.9) Asphyxia 111 (11.9) Exsanguination 003 (00.3) Other non-cardiac 127 (13.7) Time from collapse to ROSC, min, median (IQR) 31 (22-42)0 Glucose after ROSC, mg/dl, median (IQR) 242 (172-313) GCS after ROSC, median (range) 3 (7) IQR: interquartile range, CPR: cardiopulmonary resuscitation, Vf: ventricular fibrillation, VT: ventricular tachycardia, ROSC: return of spontaneous circulation, GCS: glasgow coma scale Table 2. Therapeutic hypothermia characteristics. n=930 Time from ROSC to start of TH, min (IQR) 101 (46-200) Target temperature, n (%) 32 C 008 (00.9) 33 C 835 (89.8) 34 C 084 (09.0) 35 C 003 (00.3) Time from start of TH to achieve target temperature, min, median (IQR) 150 (80-267)00. Duration of maintenance, min, median (IQR) 1,440 (1,290-1,440) Duration of rewarming, min, median (IQR) 708 (420-900)0. Monitor site of temperature, n (%) Rectum 571 (61.4) Esophagus 223 (24.0) Bladder 157 (16.9) Tympanic membrane 036 (03.9) Axilla 021 (02.3) ROSC: return of spontaneous circulation, TH: therapeutic hypothermia, IQR: interquartile range

752 / 대한응급의학회지 : 제 25 권제 6 호 2014 Table 3. The performance of therapeutic hypothermia and coronary angiography after return of spontaneous circulation according to the year. 2007 2008 2009 2010 2011 2012 p Time from ROSC to TH, min, median (IQR) 108 168 112 111 97 92 <0.002 (43-265) (58-168) (59-262) (53-234) (46-203) (40-175) Rewarming duration, min, median (IQR) 315 420 420 600 720 755 <0.001 (150-600) (305-848) (300-638) (360-780) (505-900) (608-1,020) Time from ROSC to angiography, hr, median (IQR) 12,820 12,981 14,083 5,659 450 236 <0.001 (924-37,200) (107-20,687) (8,345-25,715) (232-13,361) (103-7,494) (106-9,736) ROSC: return of spontaneous circulation, TH: therapeutic hypothermia, IQR: interquartile range 가가장많았으며, 84 (9.0%) 례에서는체온측정을두군데이상에서시행하였다. 저체온치료를시행하면서발생한합병증의발생빈도는 Table 4에기술하였다. 4. 심장치료및저체온치료방법 자발순환회복후시행되었던심장치료와순환보조치료의빈도는 Table 5에제시하였다. 자발순환회복후심인성쇽은 293 (31.5%) 례에서관찰되었다. 관상동맥조영술은 236 (25.4%) 례에서시행되었으나관상동맥중재술은 86 (9.2%) 례에서만시행되었다. 자발순환회복후관상동맥조영술까지시간의중앙값은 1,045 (121-12,051) 시간이었으며, 시간이흐름에따라개선되는추세를보였다 (p< 0.001) (Table 3). 저체온치료를시행하기위해다양한방법들이이용되었다 (Table 6). 저체온치료유도기에는여러가지체표냉각법과체내냉각법들이동시에적용되었으며, 758 (81.5%) 례의환자에서되먹임기능을갖춘장비들이이용되었다. 재가온의방법으로장비를이용하지않고 39 (4.2%) 례에서는수동적재가온도시행되었다. Table 4. Adverse events during therapeutic hypothermia. n=930 Hyperglycemia 431 (46.3) Pneumonia 345 (37.1) Hypotension 335 (36.0) Seizure 292 (31.4) Hypokalemia 264 (28.4) Overcooling 181 (19.5) Sepsis 136 (14.6) Bradycardia 123 (13.2) Hyperthermia after rewarming 104 (11.2) Hypoglycemia 085 (09.13) Hyperkalemia 059 (06.34) Bleeding 038 (04.08) Table 5. Coronary reperfusion therapy and other circulatory supportive therapies. n=930 Coronary angiography 236 (25.4) Percutaneous coronary intervention 086 (09.25) Thrombolysis 006 (00.65) Coronary artery bypass graft 008 (00.86) Intraaortic balloon pump 039 (04.19) Exctracoporeal membrane oxygenation 034 (03.66) Continuous renal replacement therapy 083 (08.92)

이병국외 : 우리나라에서병원전심정지후저체온치료의결과와현황 - 한국저체온치료연구회환자등록체계를이용하여 - / 753 고찰총 930례의저체온치료를받은심정지환자가등록되었는데, 249 (26.8%) 례가예후우량군에속하였으며, 556 (59.8%) 례가생존퇴원하였다. 자발순환회복후저체온치료시작까지의시간은 101 (46-200) 분이었고, 재가온에소요된시간은 708 (420-900) 분이었다. 해가지날수록저체온치료의시작시간은빨라지고재가온은천천히유지하여저체온치료행위가향상되는추세였다. 관상동맥조영술은 236 (25.4%) 례에서시행되었고, 관상동맥조영술의시행까지의시간은짧아지는추세이긴하지만여전히오랜시간이소요되었다. 소생후치료도중주로발생하는합병증은고혈당, 폐렴, 저혈압, 발작저칼륨혈증등이었다. 저체온치료의효과를증명했던두개의무작위대조군연구에서는연구대상의초기리듬이모두심실세동이었다 19,20). 제세동이필요한리듬인경우에비해초기심전도가제세동이필요하지않은리듬인경우는신경학적예후나생존율이훨씬낮은것으로알려져있으며, 제세동이필요하지않은리듬의경우는저체온치료의유용성이증명되지않아서미국심장협회도 Class IIb로권고하고있는실정이다 6,8,21,22). 38개의센터에서 986명의환자를등록시켰던환자등록연구는제세동이필요한리듬의경우 56% 의예후우량군과 61% 의생존율을보고하였으며, 1,145명의심정지환자를대상으로저체온치료의효과를비교했던 Dumas 등 8) 의연구는제세동이필요한리듬의경우 44% 가예후우량군이었음을보고하였다 21). 또 372명의심정지환자를대상으로한 Soga 등 22) 의연구는제세동이필요한리듬의경우 30일째신경학적예후가좋은환자가 66% 였는데, 이들의연구는목격된심정지만포함하였다. 본연구의결과초기심전도가제세동이필요한리듬인경우예후우량군이 60.5% 로기존의다른연구들과유사한수준을보였다. Dumas 등 8) 은초기심전도가제세동이필요하지않은심정지환자의경우저체온치료후 15% 의환자가예후우량군에 속함을보고하였다. 본연구의결과는 14.6% 의환자가예후우량군에속하여비슷한수준을보였다. Soga 등 22) 의연구와 Testori 등 10) 의연구는제세동이필요하지않은심정지환자에서저체온치료후각각 32% 와 35% 의높은비율의예후우량군을보고하였는데, 이들의연구대상은목격된심정지만을대상으로하였고, 심정지환자에대한대응체계가발달한나라들에서시행된연구들이기때문에달랐을것으로생각한다. 자발순환회복후가장적절한저체온치료의시작시간은알려져있지않다. 무작위대조군연구에서는 105 (61-192) 분이내에시작하였다 20). 동물실험결과에의하면저체온치료를지연하였을경우저체온치료의효과가감쇠된다고보고되었기에, 저체온치료를지연하는것은좋지않는것으로받아들여진다 23). 따라서, 최근에발표된저체온치료연구결과들을보면, 저체온치료시작까지의시간이 90 (60-165) 분, 57.5 (21-138) 분으로비교적빠른시간이내에시작하였다 13,21). 본연구결과도자발순환회복후 101 (46-200) 분에저체온치료를시작하였으며, 시간이지날수록점점짧아지는경향을나타내는것으로보아점차더적극적으로저체온치료를시행한것으로볼수있다. 하지만, 저체온치료의시작시간은 Nielsen 등 21) 의연구에서도예후와유의한연관관계를나타내지는않았다. 예후와관련이있는다른변수들의영향을감안한다면예후에큰영향을미치는요소는아닐수도있고, 많은기관들에서가능한빠르게저체온치료를시작하려는치료지침을갖고있기때문에큰차이를내는요소가아닐수도있다. 저체온치료의시작부터목표체온까지도달하는시간인유도기간을가능한짧게함으로써발생할수있는합병증을줄이는것역시저체온치료에서강조되는점이다 24). 무작위대조군연구는자발순환회복후목표체온에도달하는데에 8 (4-16) 시간이소요되었고, 또다른연구에서는 260 (178-400) 분이소요되었다 20,21). Yokoyama 등 13) 은환자등록체계정보를이용한연구에서저체온치료시작으로부터목표체온도달까지의시간을 3.0 (1.3-5.8) 시간으로보고하였는데, 본연구의결과는 150 (80-267) 분으로 Table 6. Therapeutic hypothermia methods. Induction Maintenance Rewarming External cooling Blanket 344 (37.0) 320 (34.4) 295 (31.7) Ice bag 348 (37.4) 093 (10.0) 026 (02.8) Adhesive pad 193 (20.8) 193 (20.8) 176 (18.9) Garment 078 (08.4) 073 (07.8) 065 (07.0) Fan 062 (06.7) 008 (00.9) 003 (00.3) Linen 042 (04.5) 000 (00.0) 012 (01.3) Internal cooling Cold saline 636 (68.4) 073 (07.8) 021 (02.3) Intravascular catheter 261 (28.1) 265 (28.5) 247 (26.6) Lavage 074 (08.0) 033 (03.5) 000 (00.0) ECMO 015 (01.6) 015 (01.6) 010 (01.1) ECMO: extracorporeal membrane oxygenation

754 / 대한응급의학회지 : 제 25 권제 6 호 2014 크게차이가나지는않았다. 최적의저체온치료유지기간도아직밝혀지지는않았지만, 미국심장협회권고안은 12~24시간으로발표하였다 6). 이는두개의무작위대조군연구에서 12시간과 24시간동안저체온치료를유지했기때문이다 19,20). 이들의연구이외에도다수의연구들은유지기간을 12~24시간으로유지하였다 10,25-27). 일본의환자등록체계연구에서는 25 (24-43) 시간으로다른연구들보다긴시간동안유지하였지만예후와의연관성은없었다 13). 하지만, 한연구에서는 18시간이상목표체온이잘유지된군이그렇지않은군에비해신경학적예후가더좋다고보고하였다 11). 이는유지기간의시간뿐만아니라목표체온이내로체온을조절하는것또한중요한요소임을의미하기도한다. 유지기간이종료되면정상체온까지재가온을시행한다. 재가온기간동안에도전해질불균형과같은합병증이발생할수있기때문에, 예후와의연관성은밝혀진바가없지만가능한천천히재가온하는것이원칙이다 24). 미국심장협회권고안에는재가온에대한구체적언급은없으나, 많은연구들에서재가온은시간당 0.25-0.5 C 씩올리는방법을사용했다 6,8,9,12). 본연구에서도재가온에걸리는시간이 708 (420-900) 분으로기존의연구들과유사한속도로재가온을시행하였으며, 시간이지날수록재가온에소요된시간이증가됨을확인되었는데, 이는재가온의원칙에충실했음을반영한다. 저체온치료와더불어소생후치료의큰범주는관상동맥재관류이다 6). 심정지후관상동맥조영술의유용성에대해서는이견이있긴하지만, 저체온치료와병행하는데에큰어려움이없는것으로밝혀져있다 21,28). 본연구에서는심인성심정지의 41.8% 의환자에게관상동맥조영술을시행하였지만, 관상동맥조영술시행까지의시간이너무오래걸렸기때문에소생후치료로서관상동맥조영술이시행되었다고보기힘들다. 시간이지날수록점차개선되고있는중이지만, 여전히미진하여개선의여지가많은사항이다. 22개기관에서 765명의환자를포함하여합병증과예후와의관계를분석한연구에서는폐렴 (48%), 고혈당 (37%), 발작 (24%) 등이높은빈도로나타났고, 고혈당과항발작제의사용이사망과관련이있는것으로보고하였다 29). 저체온치료를받았던심정지환자를대상으로한 63개의연구를정리한메타분석에서는고혈당 (52.4%), 폐렴 (38.0%), 저칼륨혈증 (33.7%), 저혈압 (20.8%), 등이높은빈도의합병증이었음을보고하였다 30). 본연구에서는고혈당 (46.3%), 폐렴 (37.1%), 저혈압 (36.0%), 발작 (31.4%), 저칼륨혈증 (27.4%) 등이높은빈도를나타났다. 합병증에대한정의가달랐기때문에다른연구와정확하게비교하기에는어려움이있지만, 고혈당과폐렴은다른연구들과마찬가지로가장높은빈도의발생률을나타냈고, 저혈압과발작의빈도는다른연구들보다높은빈도로나타났다. 본연구의제한점은다음과같다. 첫째, 본연구는저체온치료를받은환자들만을대상으로하였기때문에저체온치료의유용성에대해서검증하지는못했다. 둘째, 본연구는다기관이참여한연구이기는하지만, 기관들대부분이대학병원이며, 2차혹은 3차의료기관이고, 많은기관들이수도권에위치하여선택편견의가능성이높다. 세째, 입력정보를임상시험요원과관리자가검토하여수정하도록하였지만의무기록을바탕으로입력하기때문에누락된부분과결측치가존재하며, 이또한결과에영향을미칠수있다. 결 전체환자의 59.8% 가생존퇴원하였으며, 26.8% 의환자는좋은신경학적상태로퇴원하였다. 저체온치료의시작시간과재가온시간은치료원칙에비추어잘유지되었으며, 부족했던점은시간이지날수록향상되고있었다. 관상동맥조영술을시행하는시간도향상되고있다. 고혈당과폐렴이가장빈발하는합병증으로나타났다. 론 참고문헌 01. Moulaert VR, Verbunt JA, van Heugten CM, Wade DT. Cognitive impairments in survivors of out-of-hospital cardiac arrest: a systematic review. Resuscitation. 2009;80: 297-305. 02. Busto R, Globus MY, Dietrich WD, Martinez E, Valdes I, Ginsberg MD. Effect of mild hypothermia on ischemiainduced release of neurotransmitters and free fatty acids in rat brain. Stroke. 1989;20:904-10. 03. Chopp M, Knight R, Tidwell CD, Helpern JA, Brown E, Welch KM. The metabolic effects of mild hypothermia on global cerebral ischemia and recirculation in the cat: comparison to normothermia and hyperthermia. J Cereb Blood Flow Metab. 1989;9:141-8. 04. Natale JA, D'Alecy LG. Protection from cerebral ischemia by brain cooling without reduced lactate accumulation in dogs. Stroke. 1989;20:770-7. 05. Sterz F, Leonov Y, Safar P, Johnson D, Oku K, Tisherman SA, et al. Multifocal cerebral blood flow by Xe-CT and global cerebral metabolism after prolonged cardiac arrest in dogs. Reperfusion with open-chest CPR or cardiopulmonary bypass. Resuscitation. 1992;24:27-47. 06. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S768-86.

이병국외 : 우리나라에서병원전심정지후저체온치료의결과와현황 - 한국저체온치료연구회환자등록체계를이용하여 - / 755 07. Mikkelsen ME, Christie JD, Abella BS, Kerlin MP, Fuchs BD, Schweickert WD, et al. Use of therapeutic hypothermia after in-hospital cardiac arrest. Crit Care Med. 2013;41: 1385-95. 08. Dumas F, Grimaldi D, Zuber B, Fichet J, Charpentier J, Pene F, et al. Is hypothermia after cardiac arrest effective in both shockable and nonshockable patients?: insights from a large registry. Circulation. 2011;123:877-86. 09. Lundbye JB, Rai M, Ramu B, Hosseini-Khalili A, Li D, Slim HB, et al. Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms. Resuscitation. 2012;83:202-7. 10. Testori C, Sterz F, Behringer W, Haugk M, Uray T, Zeiner A, et al. Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms. Resuscitation. 2011;82:1162-7. 11. Shinozaki K, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Watanabe E, et al. Duration of well-controlled core temperature correlates with neurological outcome in patients with post-cardiac arrest syndrome. Am J Emerg Med. 2012;30:1838-44. 12. Kim JJ, Yang HJ, Lim YS, Kim JK, Hyun SY, Hwang SY, et al. Effectiveness of each target body temperature during therapeutic hypothermia after cardiac arrest. Am J Emerg Med. 2011;29:148-54. 13. Yokoyama H, Nagao K, Hase M, Tahara Y, Hazui H, Arimoto H, et al. Impact of therapeutic hypothermia in the treatment of patients with out-of-hospital cardiac arrest from the J-PULSE-HYPO study registry. Circulation J. 2011;75:1063-70. 14. The Italian Cooling Experience (ICE) Study Group. Earlyversus late-initiation of therapeutic hypothermia after cardiac arrest: Preliminary observations from the experience of 17 Italian intensive care units. Resuscitation. 2012;83: 823-8. 15. Wolfrum S, Radke PW, Pischon T, Willich SN, Schunkert H, Kurowski V. Mild therapeutic hypothermia after cardiac arrest? A nationwide survey on the implementation of the ILCOR guidelines in German intensive care units. Resuscitation. 2007;72:207-13. 16. Bouwes A, Kuiper MA, Hijdra A, Horn J. Induced hypothermia and determination of neurological outcome after CPR in ICUs in the Netherlands: Results of a survey. Resuscitation. 2010;81:393-7. 17. Kim JY, Shin SD, Ro YS, Song KJ, Lee EJ, Park CB, et al. Post-resuscitation care and outcomes of out-of-hospital cardiac arrest: A nationwide propensity score-matching analysis. Resuscitation. 2013;84:1068-77. 18. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291:870-9. 19. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-63. 20. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002;346:549-56. 21. Nielsen N, Hovdenes J, Nilsson F, Rubertsson S, Stammet P, Sunde K, et al. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2009;53:926-34. 22. Soga T, Nagao K, Sawano H, Yokoyama H, Tahara Y, Hase M, et al. Neurological benefit of therapeutic hypothermia following return of spontaneous circulation for out-of-hospital non-shockable cardiac arrest. Circulation J. 2012;76:2579-85. 23. Kuboyama K, Safar P, Radovsky A, Tisherman SA, Stezoski SW, Alexander H. Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: a prospective, randomized study. Crit Care Med. 1993;21:1348-58. 24. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. 2009;37:1101-20. 25. Busch M, Soreide E, Lossius HM, Lexow K, Dickstein K. Rapid implementation of therapeutic hypothermia in comatose out-of-hospital cardiac arrest survivors. Acta Anaesthesiol Scand. 2006;50:1277-83. 26. Kliegel A, Janata A, Wandaller C, Uray T, Spiel A, Losert H, et al. Cold infusions alone are effective for induction of therapeutic hypothermia but do not keep patients cool after cardiac arrest. Resuscitation. 2007;73:46-53. 27. Merchant RM, Abella BS, Peberdy MA, Soar J, Ong ME, Schmidt GA, et al. Therapeutic hypothermia after cardiac arrest: unintentional overcooling is common using ice packs and conventional cooling blankets. Crit Care Med. 2006;34:S490-4. 28. Reynolds JC, Callaway CW, El Khoudary SR, Moore CG, Alvarez RJ, Rittenberger JC. Coronary angiography predicts improved outcome following cardiac arrest: propensity-adjusted analysis. J Intensive Care Med. 2009;24:179-86. 29. Nielsen N, Sunde K, Hovdenes J, Riker RR, Rubertsson S, Stammet P, et al. Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Crit Care Med. 2011;39:57-64. 30. Xiao G, Guo Q, Shu M, Xie X, Deng J, Zhu Y, et al. Safety profile and outcome of mild therapeutic hypothermia in patients following cardiac arrest: systematic review and meta-analysis. Emerg Med J. 2012;30:90-100.