<30315FB1E8C5C2C7F62E687770>

Transcription

1 REVIEW ARTICLE pissn eissn THE KOREAN JOURNAL OF PANCREAS AND BILIARY TRACT 급성췌장염진료권고안 : 개발목적과과정 김태현, 김진홍, 서동완, 이태훈, 이상협, 고동희 1 원광대학교의과대학내과, 2 아주대학교의과대학내과, 3 울산대학교의과대학서울아산병원내과, 4 순천향대학교의과대학천안병원내과, 5 서울대학교의과대학내과학교실및간연구소, 6 한림대학교의과대학동탄병원내과 Clinical Practice Guidelines for Acute Pancreatitis: Purpose and Process of Guidelines Tae Hyeon Kim, M.D. 1, Jin Hong Kim, M.D. 2, Dong Wan Seo, M.D. 3, Tae Hoon Lee, M.D. 4 Sang Hyub Lee, M.D. 5, and Dong HeeKoh, M.D. 6 1 Department of Internal Medicine, Wonkwang University College of Medicine, Iksan 2 Department of Gastroenterology, Ajou University School of Medicine, Suwon 3 Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 4 Division of Gastroenterology, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Cheonan Hospital, Cheonan 5 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea 6 Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea Acute pancreatitis is a common and potentially lethal disease that is associated with significant morbidity and consumes enormous health care resources. There was still no the current domestic standard guidelines for acute pancreatitis. To provide a framework for clinicians to manage acute pancreatitis and to improve national health care, guidelines have been developed by the Korean Pancreatobiliary Association. These guidelines consisted of 39 consensus statements for the diagnosis (n=11), the assessment of the severity (n=6), initial management (n=9), the treatment of necrotizing pancreatitis and local complication (n=13) of acute pancreatitis were developed. In this article, we will describe the purpose and process of the formation of the guidelines. Key words: acute pancreatitis, guideline, clinicians 서론 1) 급성췌장염은임상적으로경증에서중증까지다양하다. Correspongding author. 김태현전북익산시신용동 원광대학병원소화기내과 Tel: 063) [email protected] 대부분경증으로 3-5일내에호전되지만중증의경우에는가성낭종, 췌장궤사, 농양형성등의국소합병증뿐만아니라전신염증반응으로다발성장기부전및사망에이를수있다. 중증췌장염의사망률은매우높아무균괴사성췌장염은 10%, 감염성췌장염은 25-30% 에이른다. 1 조기에급성췌장염을정확하게진단하고초기에중증경과를보일것으로예측되는환자를선별하여집중치료하는것은국민보건향상에매우중요하다. 그러나미국, 영국, 유 1

2 김태현외 5 인 2 럽, 일본에는가이드라인이개발되어사용되고있지만, 국내에적합한급성췌장염의진단과치료에관한가이드라인없는실정이다. 이에대한췌담도학회에서는급성췌장염의진료에도움이될수있는가이드라인을개발하였다. 본고에서는이가이드라인의소개에앞서가이드라인의개발목적과과정등을소개하고자한다. 1. 가이드라인개발취지와목적급성췌장염은 3차병원뿐만아니라 1,2차병원에서도진료할수있는흔한질환이지만진단, 치료에관한국내의료환경에맞는진료가이드라인이없는실정이다. 또한각병원마다급성췌장염에대한진료형태가매우다양하다. 따라서국내의충분한진료경험과국내외자료를바탕으로한국실정에맞는급성췌장염진단과치료에관한가이드라인개발이필요하다. 급성췌장염의치료근거를제시하기위한국내문헌은매우제한적이어서문헌검색을통하여외국에서제안하는가이드라인과근거문헌들을기반으로우리나라의료실정에적합하고임상적으로실행이가능한가이드라인을개발하고자하였다. 본가이드라인은급성췌장염의진단및치료에대한포괄적이고실제적인가이드라인이다. 2. 가이드라인을적용할대상집단및가이드라인이용자급성췌장염으로진단된성인남녀환자가본가이드라인의주된대상집단이며, 급성췌장염으로인한전신염증반응을가진환자뿐만아니라국소합병증, 즉췌장주위수액고임 (peripancreatic fluid collecton), 췌장괴사 (pancreatic necrosis), 가성낭종 (pseudocyst), 췌장농양 (pancreatic abscess) 등의합병증을가진환자들을포함 한다. 1차, 2차및 3차의료기관의다양한의료분야에서진료하고있는모든의료진에게도움이되는권고안을제시하고자하였다. 또한이는전공의교육을위한교육자료로도활용될수있다. 궁극적으로국내급성췌장염의진단과치료수준향상을통하여환자의삶의질을개선하고국민보건향상에도움을주고자하였다. 3. 가이드라인의개발과정국내급성췌장염의가이드라인개발의필요성에대한췌담도학회회원들의요구에편승하여 2012년 3월대한췌담도학회회장 ( 김진홍 ) 및임원진을중심으로가이드라인개발사업을수립하였다. 이사업을대한췌담도학회학술위원회에서학술위원장을중심으로가이드라인개발전략을수립하였다. 국내의급성췌장염가이드라인개발의가장큰문제점은국내자료가제한적이고, 역학적특성이다른일본, 북미와유럽의연구자료가대부분이었다는점이다. 급성췌장염에관한해외진료지침들의질 (quality) 을 Grill, Shaneyfelt, Agree도구들을이용하여평가한보고에서최근발표된미국, 영국, 이탈리아및일본의진료가이드라인이비교적높은점수를받은것으로평가되었다. 2 이진료가이드라인들을참고하여최근발표된국내외중요문헌을고찰하여학술위원회에서여러차례회의를거쳐임상현장에서반드시필요한급성췌장염의진단, 중등도평가, 초기치료, 괴사성췌장염및국소합병증치료에대한가이드라인을개발하기로계획하였다. 비교연구가부족하거나논란이큰부분은본가이드라인에서제외하였고, 일부근거가부족한경우에는임상적으로의의가있고전문가가일치하는부분에서는전문가들의합의과정을거쳐가이드라인에포함하였다. 각항목의권고등급은 Table 1. Grades of recommendation Grade of recommendation A B C Contents Recommended strongly to perform Evidence is strong and clear clinical effectiveness can be expected Recommended to perform Evidence is moderate or strong, although evidence of effectiveness is sparse Evidence is sparse, but may be considered to perform Effectiveness can possibly be expected Considered to be unacceptable D There is evidence to deny effectiveness(to show harm) Modifications from the JPN Guidelines

3 급성췌장염진료권고안 : 개발목적과과정 3 Table 1을기준으로판단하였다. 2012년추계대한췌담도학회에서담당학술위원들이 4가지제목에대한최신지견과진료가이드라인을발표하여학회회원들의의견을수렴하였다. 학회에서제시된의견과국내의췌장질환전문가들의의견을수렴하여각가이드라인을수정보완을하였다. 대한췌담도학회지에발표할원고는 4분야 ( 급성췌장염의진단, 급성췌장염의중등도평가, 급성췌장염의초기치료, 괴사성췌장염과국소합병증 ) 에대한가이드라인 (39 항목 ) 과그근거을제시하는형태로기술하였다. 즉가이드라인 39개항목은급성췌장염의진단은 11개항목, 중증도평가는 6개항목, 초기치료는 9개항목, 국소합병증및괴사성췌장염의치료는 13개항목으로구성되었다. 이권고안에대하여대한췌담도학회평생회원들의동의정도를알아보고자설문지조사를하여 105명이응답하였다. 이설문지의응답결과를권고등급과함께가이드라인에기술하였다. 이가이드라인에대한동의정도를 4개의척도를이용하여질문하였고다음과같았다. 1) 전적으로동의함, 2) 대체로동의함, 3) 일부동의함, 4) 전적으로동의하지않음. 본가이드라인개발은외부재정지원없이이루어졌으며, 이진료가이드라인개발과정에참여한모든구성원은이해상층의문제가없다. 이진료가이드라인은임상의의재량권을규제하는것이아니라급성췌장염의진단과치료에있어서일반적인내용을제시하는것으로이해되어야한다. 급성췌장염환자에대한진료행위는담당의사가개개환자의여러상황과병원시설을종합적으로고려하여환자나보호자와충분하게상의후결정하여야한다. 따라서본가이드라인이진료비지급의적절성평가기준이나, 의료분쟁에있어서법률적판단이나절대적기준으로사용되는것은부적절하다. 향후급성췌장염의병태생리, 진단, 중등도평가, 치료대책에대한연구들이더많이진행 되어임상적근거가변화되면진료가이드라인은개정될것이다. 국문초록 급성췌장염은임상의들이흔히진료할수있는질환으로임상적으로경증에서중증까지다양하고, 중증의경우에는다발성장기부전및사망에이를수있는치명적인질환이다. 외국에서는이질환에대한가이드라인이개발되어사용되고있지만, 국내에적합한급성췌장염의진단과치료에관한가이드라인없는실정이다. 이에대한췌담도학회에서는급성췌장염의진료와국민보건향상에도움이될수있는가이드라인을개발하였다. 가이드라인은 4 분야 39개의항목으로구성되어있다. 즉 4 분야는급성췌장염의진단 (11개), 중증도평가 (6개), 초기치료 (9개), 국소합병증및괴사성췌장염의치료 (13개) 로구성되었다. 본고에서는이가이드라인의소개에앞서가이드라인의개발목적과과정등을소개하였다. 색인단어 : 급성췌장염, 가이드라인, 임상의 참고문헌 1. Pandol SJ, Saluja AK, Imrie CW, Banks PA. Acute pancreatitis: bench to the bedside. Gastroenterology 2007;132: Loveday BP, Srinivasa S, Vather R, et al. High quantity and variable quality of guidelines for acute pancreatitis: a systematic review. Am J Gastroenterol 2010;105: Takada T, Hirata K, Mayumi T, et al. Cutting-edge information for the management of acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17:3-12.

4 REVIEW ARTICLE pissn eissn THE KOREAN JOURNAL OF PANCREAS AND BILIARY TRACT 급성췌장염진료권고안 : 급성췌장염의진단 고동희, 김종혁, 이진, 최호순 1 한림대학교의과대학내과학교실, 1 한양대학교의과대학내과학교실 Clinical Practice Guidelines for Acute Pancreatitis: The Diagnosis of Acute Pancreatitis Dong Hee Koh, M.D., Jong Hyeok Kim, M.D., Jin Lee, M.D., Ho Soon Choi, M.D. Department of Internal Medicine, Hallym University College of Medicine, Hwaseong, Korea 1 Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea There is general acceptance that a diagnosis of acute pancreatitis requires two of the following three features: 1) abdominal pain characteristic of acute pancreatitis, 2) serum amylase and/or lipase 3 times the upper limit of normal, and 3) characteristic findings of acute pancreatitis on ultrasonography, CT or MRI. Other pancreatic diseases and acute abdomen have been ruled out are diagnosed. In pancreatic enzymes, serum lipase may be preferable because it is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis. Contrast-enhanced CT scan is the best imaging technique to exclude conditions that masquerade as acute pancreatitis, to diagnose the severity of acute pancreatitis, and to identify complications of pancreatitis. After the diagnosis of acute pancreatitis has been made, its etiology should be made clear to decide treatment policy of acute pancreatitis or to prevent the recurrence of pancreatitis. The etiology of acute pancreatitis in an emergency situation should be assessed by clinical history, laboratory tests such as serum liver function tests, measurement of serum calcium and serum triglycerides and ultrasonography. A differentiation of gallstone-induced acute pancreatitis should be given top priority in its etiologic diagnosis because it is related to the decision of treatment policy. Early ERCP should be performed in patients with gallstone pancreatitis if a complication of cholangitis and a prolonged passage disorder of the biliary tract are suspected. Cholecystectomy should be considered after recovery from an attack of gallstone pancreatitis during the same hospital stay. In severe gallstone-induced acute pancreatitis, cholecystectomy should be delayed until there is sufficient resolution of the inflammatory response and clinical recovery. Key words: acute pancreatitis, guidelines, diagnostic criteria, gallstone pancreatitis 서론 1) 급성췌장염은췌장의가역적인염증성질환으로, 여러 Correspongding author. 고동희한림대학교동탄성심병원소화기내과경기도화성시석우동 40 ( ) Tel : , Fax : [email protected] 원인에의해선방세포 (acinar cell) 가손상되어췌장에국소적염증이발생하여췌장주변조직과타장기까지손상을미치는질환이다. 1 급성췌장염은대부분경증으로양호한경과를보이지만, 약 15~20% 정도에서는중증으로진행되어 20% 내외의사망률이보고되기도한다. 2 그러므로, 췌장염으로인한사망률과이환율을낮추기위해전세계적으로진단과치료에대해많은연구가진행되고있다. 급성췌장염은급성의상부복통과췌장효소수치의상승, 췌장염의영상소견이있을때진단하게된다. 그러나, 4

5 급성췌장염진료권고안 : 급성췌장염의진단 5 전형적인증상과영상소견, 췌장효소수치의급격한상승등이쉽게나타나는경우도있지만, 검사결과가모호하거나다른복부질환과의감별이필요하여진단이어려운경우도많다. 정확한진단과원인에대한감별이되어야급성췌장염의중등도를파악하고적절한치료를할수있기때문에췌장염의치료는우선정확한진단이매우중요하다. 췌장염에대한많은연구를바탕으로세계여러나라에서이에대한가이드라인을만들어사용하고있으며그중에진단에대한기준도포함되어있다. 3-7 최근, 일본 4, 이탈리아 6, 미국 7 및영국 8 에서발표한급성췌장염의가이드라인은어느정도적절하다고평가되고있으며, 이에이들가이드라인을바탕으로진단방법과기준에대한최근연구결과등을검토및비교해보고우리나라에맞는급성췌장염의진단에대한권고사항을제시하고자한다. 본론 1. 진단기준급성췌장염의진단기준은어느나라에서나비슷하게제시하고있다. 4,5 이런진단기준은중증의급성췌장염환자가의식이없는상태에서내원하거나증상발생과내원시기에차이에따른췌장효소수치가정상인경우에도진단을내릴수있다. 그러나, 이런진단기준에부합되더라도다른급성복통을일으킬수있는질환 ( 위장관의천공, 급성담낭염, 장마비, 장간막동맥허혈혹은경색, 급성대동맥박리, 급성심근경색 ) 에대한감별은반드시필요하다. 권고사항 1. 급성췌장염의진단기준은 (1) 상복부의급성복통과압통 (2) 혈액췌장효소수치의상승 ( 아밀라아제그리고 / 또는리파아제 정상상한치의 3배 ) (3) 복부초음파, 복부 CT, 혹은복부 MRI에서급성췌장염의소견위의세가지중에 2가지이상이면서다른췌장질환이나급성복통을일으키는질환이감별된다면급성췌장염으로진단할수있다. -권고등급: A -동의수준: 전적으로동의함 (79%), 대체로동의함 (19%), 일부동의함 (1%), 전적으로동의하지않음 (1%). 2. 임상증상과징후급성췌장염을의심하는데있어가장중요한증상은급성췌장염에부합되는상복부의급성복통이다. 약 90% 이상의급성췌장염환자에서복통을호소하며, 40%~70% 에서는등으로방사되는전형적인복통을호소한다. 8,9 이복통의특징은시작과동시에 30분안에빠르게최고조로이르게되어참기어려울정도의통증을유발하며호전없이 24시간이상지속된다. 6 신체검사에서는복부에심한압통이있으면서때때로복부의긴장 (abdominal guarding) 이동반된다. 10 한연구에의하면통증은주로상복부에서나타나고그다음으로전반적인복통을호소하는경우가많고, 압통은주로전반적인압통을호소하며다음으로상복부나우상복부압통을호소하는경우가많았다. 11 드물지만모든환자에서복통이나타나는것은아니다. 11 중증의급성췌장염환자를분석한연구를보면, 30-40% 정도에서전형적인복통증세를나타내지않아부검으로급성췌장염이진단되었다. 이는복통이없이혼수상태나다발성장기부전상태로내원하여진단이어려웠기때문이다. 9,12 복통외에나타나는증상과징후는식욕부진, 오심과구토, 고열, 장음의감소등이있다. 8 권고사항 1. 급성췌장염을의심하는데있어가장중요한임상증상과징후는급성췌장염에부합되는상복부의급성통증과압통이다 -권고등급: A -동의수준: 전적으로동의함 (57%), 대체로동의함 (37%), 일부동의함 (5%), 전적으로동의하지않음 (1%). 3. 생화학적검사임상적으로급성췌장염이의심될때혈청의췌장효소상승은진단에중요한역할을한다. 췌장효소중에전세계적으로주로사용되고있는것은혈청아밀라아제검사이다. 그러나, 여러비교연구의결과를보면리파아

6 고동희외 3 인 6 Table 1. Causes of increased amylase and lipase levels Amylase Acute pancreatitis Lipase Acute pancreatitis Diseases that might mimic acutepancreatitis Pancreatic pseudocyst Chronic pancreatitis Pancreatic carcinoma Biliary tract disease (cholecystitis, cholangitis, choledocholithiasis) Intestinal obstruction, pseudoobstruction,ischemia, orperforation Acute appendicitis Pancreatic pseudocyst Chronic pancreatitis Pancreatic carcinoma Biliary tract disease (cholecystitis, cholangitis, choledocholithiasis) Intestinal obstruction, pseudoobstruction,ischemia, orperforation Acute appendicitis Ectopic pregnancy Other disorder Renal failure Parotitis Macroamylasemia Ovarian cyst or cystic neoplasm Carcinoma of the lung Diabetic ketoacidosis Human immunodeficiency virusinfection Head trauma with intracranialbleeding Renal failure From ref. 9 제가아밀라아제에비해민감도는비슷하지만특이도는더우월한것으로보고하고있다. 13,14 그러므로, 급성췌장염의진단을위해서는혈청아밀라아제보다리파아제가더추천된다. 4-7 (1) 혈청아밀라아제혈청아밀라아제는응급으로검사결과를확인할수있어서과거부터급성췌장염의진단에많이사용되고있다. 혈청아밀라아제의근원은췌장이약 40% 정도를차지하고있고나머지는주로침샘과다른부분이맡고있다. 그러므로, 혈청아밀라아제상승은급성췌장염이아닐수있어다른질환이나상태에대해서고려해야한다 (Table 1). 혈청아밀라아제민감도와특이도는기준에따라변하게되는데기준을정상의상한치에두면민감도는 91.7~100% 이고특이도는 71.6~97.6% 인데반하여, 기준을높여 1000 IU/L로하면특이도는 100% 까지올라가나민감도는 60.9% 까지낮아진다. 4 그러므로, 대부분의교과 서나전문가들의의견은적어도정상상한치의 3배이상을제시하고있고, 이렇게하였을때응급실에내원한 500명의환자를대상으로한전향적연구에서민감도는 85%, 특이도는 91% 였다. 15 혈청아밀라아제는급성췌장염이라도상승하지않는경우가있는데, 이는혈청아밀라아제가급성췌장염발생후바로감소하기때문에경한급성췌장염에서혈액검사시기가늦어진경우, 만성췌장염특히알코올성만성췌장염의급성악화의경우, 중성지방의상승이검사를방해하여고중성지방혈증이있는경우에는높게나오지않을수있다 반대로혈청아밀라아제는신부전이있거나 macroamylasemia 같은췌장질환이아닌경우에도상승할수있다 (Table 2). (2) 혈청리파아제혈청리파아제는췌장염의진단에있어서혈청아밀라아제보다우수한것으로알려져있다. 왜냐하면, 특이도에

7 급성췌장염진료권고안 : 급성췌장염의진단 7 Table 2. Causes of acute pancreatitis Biliary Gallstones, microlithiasis, "biliary sludge" Alcohol Anatomic variants Pancreas divisum, choledochal cyst, duodenal duplication,santorinicele, duodenal diverticula Mechanical obstructions to flow of pancreatic juice Ampullary: benign and malignant tumors, stricture or dysfunctionof SOD Ductal: stones, strictures, masses(including tumors), mucus(eg, inintraductal papillary mucinous neoplasms), parasites (Ascaris) Metabolic Hypercalcemia, hypertriglyceridemia Drugs Toxins Trauma Blunt and penetrating, instrumentation(ercp, pancreatic biopsy) Ischemia Hypotension, arteritis, embolic Hypothermia Infections Viral(mumps, Coxsackie A, human immunodeficiency virus) Bacterial/other: M tuberculosis, mycoplasma Parasites(Ascaris) Venoms(spider, Gila monster) Autoimmune With or without associated autoimmune diseases(siccasyndrome, primary sclerosing cholangitis, autoimmunehepatitis, celiac disease) Genetic(familial, sporadic) Idiopathic From ref. 9 있어서혈청리파아제는췌장외에는리파아제에영향을줄다른중요한근원이되는장기가없고, 민감도에있어서혈청아밀라아제에비해더오래동안수치가상승되어있기때문이다. 20 연구에따라차이가있지만급성췌장염의진단에대한민감도는 85~100%, 특이도는 84.7~99.0% 정도로알려져있다. 13 혈청리파아제도급성췌장염이외의상태에서도상승할수있는데특히신부전이있을때아밀라아제와마찬가지로신장기능의저하에의해제거기능이감소하여수치가상승하게된다. 크레아티닌청소율이 13 ml/min ~ 39 ml/min 에서아밀라아제는반수이상, 리파아제는 1/4 정도에서증가되어있다. 21 이또한리파아제가아밀라아제보다우수한점이다. 혈청아밀라아제와리파아제를같이검사하였다고해서진단의정확도가높아진다는보고는없다. 췌장염이한번진단되면두검사를매일검사하는것은병의경과나예후를판단하는것에큰도움을주지않는다. (3) 다른췌장효소검사진단방법으로현재여러가지췌장효소검사가혈액이나소변으로측정되고있다. 이에해당하는것이아밀라아제 isoenzyme, phospholipase A 2, elastase1, anionic trypsinogen(trysinogen-2) 등이있다. 22 최근몇몇의연구에서다른췌장효소검사가좋은임상결과를보여주고있으나여전히임상적으로사용하고있지는않다. 권고사항 1. 급성췌장염을진단하는데있어현재많이사용되고있는생화학적검사는혈청아밀라아제이지만, 혈청리파아제검사가더급성췌장염의진단에유용하다. -권고등급: A -동의수준: 전적으로동의함 (43%), 대체로동의함 (44%), 일부동의함 (12%), 전적으로동의하지않음 (1%).

8 고동희외 3 인 8 4. 영상검사췌장효소검사의민감도나특이도가급성췌장염을진단하는데많은도움을주지만확진하는검사가아니므로수치가많이상승하지않는경우는진단하는데어려움이있을수있다. 이럴때영상검사, 특히복부 CT (Computed tomography) 가진단을확진하는데도움을준다. (1) 단순흉부와복부촬영단순흉부와복부촬영으로급성췌장염을진단할수는없다. 하지만, 이는소화관천공등의감별에도움을주며병의경과를판단하는데중요한검사이다. 그러므로, 모든급성췌장염이의심되는환자에서촬영하는것을추천한다. 4 하지만영국의가이드라인에서는추천하지않는다. 7 (2) 복부초음파복부초음파검사로췌장의비대, 췌장주변의염증변화, 복수등급성췌장염의소견을관찰할수있다. 23 하지만, 주변장관의공기로인해정확한검사를시행하기가어려운경우가있을수있다. 그러므로, 복부초음파검사의주요목적은급성췌장염의진단보다는담낭담석이나총담관담석에의한총담관의확장을확인하는데있다. 담석성급성췌장염환자에서복부초음파가담석을확인하는민감도는 70% 정도로좀낮지만, 회복후다시실시하면더좋아진다는보고가있다. 24,25 급성췌장염환자에서복부초음파검사는원인을밝히는데도움을줌으로검사하는것을추천한다. 4 하지만, 영국이나이태리등다른나라에서는진단에는큰도움을주지못하므로진단목적으로추천하고있진않다. 5,7 (3) 복부 CT 복부 CT는급성췌장염을확진하는데있어가장좋은검사이다. 4-7 다른복부질환들을감별할수있고, 췌장염의중증도를결정하고, 합병증을확인할수있는영상검사이다. 6,9 최근에는 multidetector CT (MDCT) 의사용으로정확도가증가하고있다. 급성췌장염을나타내는복부 CT 소견으로는췌장의비대, 췌장실질의불균질 (heterogeneity), 췌장주변의 stranding, 췌장주변의액체저류등이있으며, 조영제를사용하면췌장괴사를확인할수있다. 더욱이, 복부 CT 검사는급성췌장염의원인을확인하는데중요한단서를제공한다. 예를들면, 총담관에담석이보이거나, 만성췌장염환자에서췌장의석 회화가관찰되거나, 췌장암을시사하는종괴가관찰되는경우등이있다. 6 그러나, 일부연구에서 CT 촬영중에사용하는조영제가췌장의미세순환에영향을주어췌장염을악화시킨다는보고가있어논란이있다. 24,25 아직까지는이에대해확실하게결정되지는않았지만, 모든급성췌장염환자에서복부 CT 검사가필요하지는않고다른방법으로급성췌장염을진단하거나다른질환을배제하는데문제가없다면, 췌장염의중증도를가장정확하게알수있는발생 2-3일후에검사하는것이좋다. 5,9 그리고, 환자가장기부전이지속되거나, 폐혈증의소견을보이거나, 임상적으로악화되는경우췌장염발생 6-10일에추가적으로복부 CT를검사할수있다. 5 (4) 복부 MRI 복부 MRI (Magnetic resonance imaging) 검사는복부 CT 만큼이나진단에있어정확하고합병증이나췌장의괴사, 증증도평가에도좋은검사이다. 4-6,26 MRCP (Magnetic resonance cholangiopancreatography) 는담췌관의해부학구조를파악하고작은담관담석을확인할수있으며조영 MRI로는출혈성췌장괴사를감별하는데도유용하다. 27 하지만, 실제로중증의환자를상대로검사하기는어려운점이있다. (5) ERCP ERCP (Endoscopic retrograde cholangiopancreatography) 는시술과관련된합병증으로인해급성췌장염의진단을목적으로시행하지않는다. 28 단, 담석성췌장염에한해서내시경치료를고려하여시행할수있다. 4 권고사항 1. 급성췌장염을진단하는데있어복부초음파는진단에큰도움을주는검사는아니지만담석이나담도확장등의원인을밝히는데도움을주므로검사하는것을추천한다. -권고등급: B -동의수준: 전적으로동의함 (30%), 대체로동의함 (58%), 일부동의함 (11%), 전적으로동의하지않음 (0%).

9 급성췌장염진료권고안 : 급성췌장염의진단 9 2. 급성췌장염이의심되는환자에서복부 CT 검사는진단에있어서매우유용한검사이다. -권고등급: A -동의수준: 전적으로동의함 (73%), 대체로동의함 (23%), 일부동의함 (3%), 전적으로동의하지않음 (1%). 3. MRI 검사는복부 CT 만큼급성췌장염의진단과중증도를평가하기에좋은검사이다. 특히담석성췌장염이나출혈성췌장괴사진단에는복부 CT보다우월하다. -권고등급: B -동의수준: 전적으로동의함 (15%), 대체로동의함 (44%), 일부동의함 (33%), 전적으로동의하지않음 (8%). 5. 원인에대한평가급성췌장염으로진단된이후에가능한빨리원인에대한평가를시작하여야한다. 4,5,6 이는급성췌장염의원인 (Table 3) 은다양하며밝혀진원인에따라치료방침이바뀔수있기때문이다. 특히담석에의한췌장염인경우는 ERCP 시행여부를결정하여야하기때문에가장우선적으로확인하여야한다. 이런원인에대한평가로는우선환자의과거력과가족력을확인하여야한다. 담석의병력, 음주력, 고지혈증, 췌장염의병력, 췌담도계수술이나 ERCP 시술여부, 약물복용력, 감염병력, 외상등에대해확인하여야하고, 대사성질환이나자가면역성질환의병력이나가족력에대해서도확인하여야한다. 4 혈액검사로빌리루빈, ALT, AST, 알칼리인산분해요소 (alkaline phosphatase) 등을측정하여담석성췌장염을감별해야한다. 4,5 ALT가 150 IU/L이상인경우나빌리루빈, 알칼리인산분해요소, γgtp, ALT, ALT/AST중에 3 개이상증가된경우도담석성급성췌장염일가능성이높다. 29,30 중성지방이 1000 mg/dl 이상증가한경우에는고지혈증에의한췌장염가능성이높으며, 고칼슘혈증이있으면부갑성선기능항진증등도생각해보아야한다. 4,5 영상검사로는복부초음파가담낭담석이나담도확장등을확인하여원인을아는데도움을주지만주변소화관의공기로인해정확한관찰이어려우므로복부초음파에이상이없다고담석성췌장염을배제하기는어렵다. 31 복부 CT는앞에서언급한바와같이진단과동시에종양이나외상등여러가지원인에대해평가할수있지만, 담관담석의확인은민감도가 40~53% 정도로낮아서적당하지않다. 30 MRI/MRCP 는 ERCP에비해비침습적이고췌장염을악화시키지않으면서도다소조기에담관담석여부를확인할수있는좋은검사이다. 그러므로, 초음파나 CT에서담석이확인되지않지만담석성췌장염이의심될때 MRI/MRCP 검사를적극적으로고려해볼수있다. 또한이검사를통하여분할췌나담췌관합류이상같은소견도확인할수있다. 내시경초음파 (Endoscopic ultrasonography) 는총담관담석을확인하는데있어복부초음파보다우월하다. 31 내시경초음파는기존의복부초음파로총담관담석여부를확인하지못하였을때환자가안정되면검사를시행한다. 복부초음파가원인을밝히지못한경우의 59~78% 에서내시경초음파로총담관담석을진단할수있었다. 33,34 총담관담석이외에도내시경초음파는만성췌장염, 췌장암, 췌관내유두상점액종양, 담췌관합류이상, 분할췌등의진단에도도움을주며, 따라서원인을평가하는데도유용하다. 4,33,34 ERCP 는췌장염을악화시킬위험이높기때문에시행하지않는다. 하지만, 황달, 담도염등이있거나총담관담석이의심되는담석성췌장염환자에서는담석에대해치료목적으로시행할수있다. 그외에도원인을모르는재발성췌장염환자에서미세담석여부를확인하기위한담즙채취나췌장의세포진검사유두부괄약근이상여부를확인하기위한유두부압력측정 (manometry) 검사등을시행할수있으나이탈리아가이드라인에서는췌장염발생의위험성때문에추천하지않는다. 4,5,7 권고사항 1. 급성췌장염으로진단되면앞으로치료계획의수립과재발방지를위해가능한빨리원인에대한평가를시작하여야한다. -권고등급: A -동의수준: 전적으로동의함 (78%), 대체로동의함 (21%), 일부동의함 (0%), 전적으로동의하지않음 (1%).

10 고동희외 3 인 일차적으로환자의과거력과가족력을확인하고간기능검사, 칼슘, 중성지방등의혈액검사와복부초음파검사를시행하여야한다. -권고등급: C -동의수준: 전적으로동의함 (31%), 대체로동의함 (53%), 일부동의함 (14%), 전적으로동의하지않음 (1%). 6. 담석성췌장염담석성췌장염은담석에의해유두부의공통관이막혀췌장액의배출에문제가생기거나담도염과관련된염증이췌장에까지직접적으로영향을주어생긴다. 35 담석성췌장염을의심하는경우는앞에서기술한바와같이혈액검사에서 ALT가 150 IU/L 이상인경우나빌리루빈, 알칼리인산분해요소, γgtp, ALT, ALT/AST 중에 3개이상증가된경우, 29,30 복부초음파나복부 CT에서담석이보이거나총담관의확장이관찰되는경우이다. 그러므로, 담석성췌장염의진단을위해서는일차적으로혈액검사와복부초음파검사를고려하여야한다. 4,35 그러나복부초음파검사는총담관담석을관찰하기어려운점이있으므로혈액검사에이상이있지만복부초음파에서총담관을자세히관찰하기어려우면, 더민감도가높은 MRCP 나 EUS 검사를시행하여야한다. 4,6 (1) 내시경치료급성췌장염환자에서담석성췌장염이의심될때조기에 ERCP를시행하는것은항상실제임상에서결정하기어려운문제이다. 대부분의가이드라인에서담석성췌장염이강력히의심되는환자가담도염이있거나, 담도폐쇄가지속되는경우조기에 ERCP 를시행할것을추천한다. 4-7 그러나, 담석성췌장염이의심되는중증의췌장염환자에대한조기 ERCP 시행은미국과영국가이드라인에서만추천하고있다. 6-7 실제로 ERCP 와유두부절개술을시행하는것이과연얼마나이로운것에대한무작위대조군연구 (randomized controlled trial) 에대한한메타분석에따르면경증의췌장염군과중증의췌장염군으로나누어분석하였을때중증의췌장염군에서사망률의감소는보이지않았으나합병증의발생을의미있게줄였다. 36 그러나다른메타분석에서는담도염이없는췌장염환자를대상으로분석하였을때조기에시행한 ERCP 와유두부절개술은중증도와 상관없이합병증발생과사망률을감소시키지못했다. 37 최근에 Cochrane library 에서발표한메타분석에따르면담석성췌장염의조기 ERCP 시행에대해각각의세부그룹으로나누어분석하였을때중증의췌장염환자에서는사망률과합병증발생률에차이가없었으나, 담도염이있는환자는사망률과합병증이, 담도폐쇄가있는환자는국소적합병증이의미있게감소하였다. 38 시술시간에대한비교연구에서는발생후 24~48 시간이내에시행한군에서 48시간이후에시행한군에비해조기합병증이낮았고, 전반적인합병증의발생도낮았다. 39 이상의연구들로볼때조기에 ERCP 와유두부절개술을시행하는것은중증의담석성췌장염이면서담도염과같은담관의폐쇄가의심되는환자에서시행하는것이유용하겠다. 담석성췌장염환자중에담낭절제술을시행하기에는고령이거나수술위험도가높은경우에유두부절개술만시행하고담낭절제술을시행하지않고관찰하는것에대한여러논의가있었다. 실제로이에대한연구들을보면, 유두부절개술만시행한군은담낭절제술을시행한군에비해담도계의합병증의발생은증가하였지만, 췌장염의발생은크게차이가없었다. 40 무작위대조군연구에서는 70 세이상의환자 ( 평균 80세 ) 에서 17개월동안관찰하였을때두군에서모두췌장염은재발하지않았다. 하지만, 담도계합병증은유두부절개술만시행한군은 21%, 담낭절제술을시행한군은 6% 로의미있게유두부절개술만시행한군에서높았다. 그러므로, 고령의나이에도담낭절제술시행이바람직하다고결론지었다. 41 또다른연구에서도 2년동안관찰하였을때췌장염의재발은없었지만, 담도계와관련된증상의재발은 47% 와 2% 로유두부절제술만시행한군에서높았다. 42 그러므로, 담낭절제술을시행하지못하는경우가아니라면 ERCP와유두부절개술만시행하는것은추천하지않는다. 4 권고사항 1. 담석성췌장염이강력히의심되는환자에서담도염이있거나, 담도폐쇄가지속되는경우조기에 ERCP 를시행한다. -권고등급: B -동의수준: 전적으로동의함 (58%), 대체로동의함 (40%), 일부동의함 (1%), 전적으로동의하지않음 (1%).

11 급성췌장염진료권고안 : 급성췌장염의진단 담낭담석이있는담석성췌장염환자에서담낭절제술을시행하지못하는경우가아니라면 ERCP 와유두부절개술만시행하는것은추천하지않는다. -권고등급: D -동의수준: 전적으로동의함 (12%), 대체로동의함 (47%), 일부동의함 (27%), 전적으로동의하지않음 (14%). (2) 담낭절제술담석성췌장염환자는췌장염의재발을예방하기위해원인이되는담석이있는담낭을제거하여야한다. 위에서기술하였듯이담낭절제술은특별히못하는이유가없으면하는것이좋다. 하지만담낭절제술을시행하는시기에대해서는가능한빨리하자는의견과염증이해결될때까지기다렸다가하자는의견이있다. 이에대해서증상발현후 72시간이내에수술한군과 3개월이후에수술한군을비교하였을때합병증발생률과사망률에큰차이가없었다. 43 경증의담석성췌장염환자에서췌장염의복통과아밀라아제가감소하기시작하면바로복강경담낭절제술을시행한군과복통이없어지고아밀라아제가정상이되면수술을시행한군을비교하였을때합병증발생률은차이가없었고입원기간은조기에수술을시행한군이더짧았다. 44 그러나, 중등도이상의췌장염환자에서는경과를보고예정수술 (elective surgery) 로하는것이좋다. 또한수술시기는처음입원하고퇴원후에기다렸다가하는경우그사이재발할확률이높아처음입원시기에수술하는것이좋다. 45 이상의연구결과들로볼때경증의담석성췌장염의환자의경우에는증상이호전되기시작하면같은입원기간내에복강경담낭절제술을시행하는것이좋고, 중증의췌장염의경우에는염증반응이충분히해소되고임상적으로호전된후시행하는것이좋다. 3-5,7 권고사항 1. 경증의담석성췌장염환자에서증상이호전되기시작하면같은입원기간내에복강경담낭절제술을시행하고, 중증의췌장염의경우에는염증반응이충분히해소되고임상적으로호전된후시행하는것을권장한다. -권고등급: B -동의수준: 전적으로동의함 (33%), 대체로동의함 (55%), 일부동의함 (10%), 전적으로동의하지않음 (1%). 결론 최근생화학검사의발달과영상검사의발달은급성췌장염의진단에많은도움을주고있지만실제임상에서는아직도진단이어려운경우가있다. 앞에서기술한가이드라인이완벽하지는않지만급성췌장염의진단에도움을줄거라생각한다. 그리고, 진단과동시에원인에대한평가를적극적으로시행하는것이매우중요하고, 담석에의한췌장염인경우담도염이있거나담도폐쇄가의심된다면조기에 ERCP 를고려해보아야한다. 급성췌장염의진단과치료에있어서현재도계속해서새로운연구와발전이되고있다. 그러므로, 앞으로도계속해서새로운연구결과에따른새로운가이드라인이소개될것이므로올바른진단과치료를위해이에대한지속적인관심이필요하다. 국문초록 급성췌장염의진단에대해서는최근생화학검사의발달과영상의학의발달로조금씩변화하고있다. 일반적으로인정받는기준은 1) 상복부의급성복통과압통, 2) 혈액췌장효소수치의상승 ( 아밀라아제그리고 / 또는리파아제 정상상한치의 3배 ), 3) 복부초음파나복부 CT, 복부 MRI에서급성췌장염의소견위의세가지중에 2가지이상이면서다른췌장질환이나급성복통을질환을감별된다면급성췌장염으로진단할수있다. 급성췌장염을진단하는데있어현재많이사용되고있는생화학적검사는혈청아밀라아제이지만, 혈청리파아제검사가혈청아밀라아제검사보다특이도와민감도가높아더급성췌장염의진단에유용하다. 복부 CT는급성췌장염을확진하는데있어가장좋은검사로다른복부질환들을감별할수있고, 췌장염의중증도를결정하고, 합병증을확인할수있는영상검사이다. 급성췌장염으로진단되면앞으로치료계획의수립과재발방지를위해가능한빨리원인에대한평가를시작하여야한다. 일차적으로환자의과거력과가

12 고동희외 3 인 12 족력을확인하고간기능검사, 칼슘, 중성지방등의혈액검사와복부초음파검사를시행하여야한다. 담석성췌장염이강력히의심되는환자에서담도염이있거나, 담도폐쇄가지속되는경우조기에 ERCP 를시행한다. 경증의담석성췌장염환자에서증상이호전되기시작하면같은입원기간내에복강경담낭절제술을시행하고, 중증의췌장염의경우에는염증반응이충분히해소되고임상적으로호전된후시행하는것을권장한다. 색인단어 : 급성췌장염, 가이드라인, 진단기준, 담석성췌장염 참고문헌 1. Felderbauer P, M ller C, Bulut K, et al. Pathophysiology and treatment of acute pancreatitis: new therapeutictargets - a ray of hope? Basic Clin Pharmacol Toxicol 2005;97: Bank S, Sinqh P, Pooran N, Stark B. Evaluation of factors that have reduced mortality from acute pancreatitisover the past 20 years. J Clin Gastroenterol 2002;35: Uhl W, Warshaw A, Imrie C, et al. International Association of Pancreatology: IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology 2002;2: Kiriyama S, Gabata T, Takada T et al. New diagnostic criteria of acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17: Pezzilli R, Zerbi A, Di Carlo V, Bassi C, Delle Fave GF. Practical guidelines for acute pancreatitis. Pancreatology 2010;10: Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101: UK guidelines for the management of acute pancreatitis. Gut 2005;54(Suppl III):iii1-iii9. 8. Malfertheiner P, Kemmer TP. Clinical picture and diagnosis ofacute pancreatitis. Hepatogastroenterology 1991;38: Forsmark CE, Baillie J. AGA Institute Clinical Practice and Economics Committee; AGA Institute Governing Board. AGA Institute technical review on acute pancreatitis. Gastroenterology 2007;132: Kwon RS, Banks PA. How should acute pancreatitis bediagnosed in clinical practice? In: Dom ınguez-mu noz JE, ed. Clinical pancreatology for practicing gastroenterologistsand surgeons. Malden, MA: Blackwell 2005;4: Read G, Braganza JM, Howat HT. Pancreatitis: a retrospective study. Gut 1976;17: Lankisch PG, Schirren CA, Kunze E. Undetected fatal acutepancreatitis: why is the disease so frequently overlooked? Am J Gastroenterol 1991;86: Agarwal N, Pitchumoni CS, Sivaprasad AV. Evaluating tests foracute pancreatitis. Am J Gastroenterol 1990;85: Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference. Int J Pancreatol 1999;25: Kemppainen EA, Hedstrom JI, Puolakkainen PA, et al. Rapid measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis. N Engl J Med 1997;337: Clavien PA, Robert J, Meyer P, et al. Acute pancreatitis and normoamylasemia. Not an uncommoncombination. Ann Surg 1989;210: Eckfeldt JH, Kolars JC, Elson MK, Shafer RB, Levitt MD. Serumtests for pancreatitis in patients with abdominal pain. Arch PatholLab Med 1985;109: Ventrucci M, Pezzilli R, Naldoni P, et al. Serum pancreatic enzyme behavior during the course ofacute pancreatitis. Pancreas 1987;2: Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am 1990;19: Gwozdz GP, Steinberg WM, Werner M, Henry JP, Pauley C. Comparative evaluation of the diagnosis of acute pancreatitis based on serum and urine enzyme assays. Clin Chim Acta 1990;187: Seno T, Harada H, Ochi K, et al. Serum levels of six pancreatic enzymes as related to the degree of renal dysfunction. Am J Gastroenterol 1995;90: Yadav D, Agarwal N, Pitchumoni CS. A critical evaluation of laboratory tests in acute pancreatitis. Am J Gastroenterol 2002;97: Jeffrey RB Jr, Laing FC, Wing VW. Extrapancreatic spread of acute pancreatitis: new observations with real-time US. Radiology 1986;159: Balthazar EJ, Freeny PC. Contrast-enhanced computed tomography in acute pancreatitis: is it beneficial or harmful? Gastroenterology 1994;106: Plock JA, Schmidt J, Anderson SE, Sarr MG, Roggo A. Contrast enhanced computed tomography in acute pancreatitis: does contrast medium worsen its course due to impaired microcirculation? Langenbecks Arch Surg

13 급성췌장염진료권고안 : 급성췌장염의진단 ;390: Matos C, Bali MA, Delhaye M, Deviere J. Magnetic resonance imaging in the detection of pancreatitis and pancreatic neoplasms. Best Pract Res Clin Gastroenterol 2006;20: Hallal AH, Amortegui JD, Jeroukhimov IM et al. Magnetic resonance cholangiopancreatography accurately detects common bile duct stones in resolving gallstone pancreatitis. J Am Coll Surg 2005;200: Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc 1998;48: Liu CL, Fan ST, Lo CM, et al. Clinico-biochemical prediction of biliary cause of acute pancreatitis in the era of endoscopic ultrasonography. Aliment Pharmacol Ther 2005;22: Wang SS, Lin XZ, Tsai YT, et al. Clinical significance of ultrasonography, computed tomography, and biochemical tests in the rapid diagnosis of gallstone-related pancreatitis: a prospective study. Pancreas 1988;3: Liu CL, Lo CM, Chan HKF, et al. Detection of choledocholithiasis by EUS in acute pancreatitis: a prospective evaluation in 100 consecutive patients. Gastrointest Endosc 2001;54: Hallal AH, Amortegui JD, Jeroukhimov IM, et al. Magnetic resonance cholangiopancreatography accurately detects common bile duct stones in resolving gallstone pancreatitis. J Am CollSurg 2005;200: Norton SA, Alderson D. Endoscopic ultrasonography in the evaluation of idiopathic acute pancreatitis. Br J Surg 2000;87: Frossard JL, Sosa-Valencia L, Amouyal G, et al. Usefulness of endoscopic ultrasonography in patients with idiopathic acute pancreatitis. Am J Med 2000;109: Kimura Y, Arata S, Takada T et al. Gallstone-induced acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17: Moretti A, Papi C, Aratari A, et al. Is early endoscopic retrograde cholangiopancreatography useful in the management of acute biliary pancreatitis? A meta-analysis of randomized controlled trials. Dig Liver Dis 2008;40: Petrov MS, van Santvoort HC, Besselink MG, et al. Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trials. Ann Surg 2008;247: Tse F, Yuan Y. Early routine endoscopic retrograde cholangiopancreatography strategy versus early conservative management strategy in acute gallstone pancreatitis. Cochrane Database Syst Rev May 16;5:CD doi: / CD pub Acosta JM, Katkhouda N, Debian KA, et al. Early ductal decompression versus conservative management for gallstone pancreatitis with ampullary obstruction: a prospective randomized clinical trial. Ann Surg 2006;243: Kaw M, Al-Antably Y, Kaw P. Management of gallstone pancreatitis: cholecystectomy or ERCP and endoscopic sphincterotomy. Gastrointest Endosc 2002;56(1): Targarona EM, Ayuso RM, Bordas JM, et al. Randomised trial of endoscopic sphincterotomy with gallbladder left in situ versus open surgery for common bile duct calculi in high-risk patients. Lancet 1996;347: Stone HH, Fabian TC, Dunlop WE. Gallstone pancreatitis: biliary tract pathology in relation to time of operation. Ann Surg 1981;194: Boerma D, Rauws EA, Keulemans YC, et al. Wait-and-see policy or laparoscopic cholecystectomy after endoscopic sphincterotomy for bile-duct stones: a randomised trial. Lancet 2002;360: Taylor E, Wong C. The optimal timing of laparoscopic cholecystectomy in mild gallstone pancreatitis. Am Surg 2004;70: Frei GJ, Frei VT, Thirlby RC, et al. Biliary pancreatitis: clinical presentation and surgical management. Am J Surg 1986;151:

14 REVIEW ARTICLE pissn eissn THE KOREAN JOURNAL OF PANCREAS AND BILIARY TRACT 급성췌장염진료권고안 : 급성췌장염의중증도평가 이상협 1,2, 류지곤 1,2, 안동원 3, 김재환 4 1 서울대학교의과대학내과학교실및간연구소, 2 서울대학교병원내과, 3 서울대학교의과대학보라매병원내과, 4 강원대학교의학전문대학원내과 Clinical Practice Guideline for Acute Pancreatitis: The Assessment of the Severity of Acute Pancreatitis Sang Hyub Lee, M.D. 1,2, Ji Kon Ryu, M.D. 1,2, Dong-Won Ahn, M.D. 3, Jaihwan Kim, M.D. 4 1 Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea, 2 Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, 3 Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Boramae Medical Center, Seoul, Korea, 4 Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Korea The assessment of severity at the initial medical examination plays an important role in introducing adequate early treatment and the transfer of patients to a medical facility that can cope with severe acute pancreatitis. Under these circumstances, guideline for severity assessment have been prepared in various countries, including Japan, Italy, United States of America, and United Kingdom and these criteria are now being evaluated. Patients with severe acute pancreatitis are expected to be transferred to a specialist medical center or to an intensive care unit to receive adequate treatment there. In this review, we are going to suggest the guideline of Korean Pancreatobiliary Association for the adequate treatment of the patients with severe acute pancreatitis and investigation of these diseases. Key words: acute pancreatitis, severity, guideline 서론 1) 급성췌장염은췌장의급성염증과정이며흔히췌장주변조직과다른원격장기의이상이동반된다. 급성췌장염의중증도는매우다양하여췌장에만염증이발생하는경증의형태에서부터다발장기부전및사망이동반되는중 Correspongding author. 이상협, Sang Hyub Lee, MD. 서울대학교병원내과서울특별시종로구대학로 101 ( ) Tel: Fax: [email protected] 증의형태까지발생할수있다. 급성췌장염은전형적인자가치유의과정을겪는질환으로경증췌장염에서는사망률이 1% 미만인데반해, 1,2 중증췌장염에서는매우높아져서무균괴사췌장염에서는 10%, 감염괴사췌장염의경우는 25-30% 에이른다. 3 급성췌장염환자에서사망은약 50% 에서발병 2주내에발생하므로급성췌장염의적절한중증도평가는초기에중증경과를보일것으로예측되는환자를선별하여적절한치료를제공하고, 여의치않은경우향후적절한치료를제공할수있는기관으로전원하는기준을제시하는데유용하게사용될수있다. 아울러, 초기에경증또는중등도의췌장염도중증췌장염으로진행할수있기때문에 14

15 급성췌장염진료권고안 : 급성췌장염의중증도평가 15 췌장염의중증도는지속적으로평가되어야한다. 본권고안에서는급성췌장염의중증도평가와관련하여중증도평가의필요성 (necessity for severity assessment), 임상증상, 징후및혈액검사를통한중증도평가 (severity assessment based on clinical symptoms, signs and clinical laboratory tests), 영상검사를통한중증도평가 (severity assessment based on diagnostic imaging), 중증도판정기준을이용한평가 (severity assessment based on scoring system) 및전원기준 (transfer criteria) 의항목에지금까지발표된임상연구결과와외국의여러권고안들을바탕으로, 우리나라에적합한급성췌장염의중증도평가에대한권고안을제시하고자한다. 아울러, 권고안에제시된근거평가의등급및권고등급은앞에서기술한것과동일하다. 본론 1. 중증도평가의필요성 (necessity for severity assessment) 급성췌장염의임상양상은다양하여중증도에대한주관적인평가는쉽지않아서현재까지중증췌장염의예측은다인자를이용한몇가지의중증도판정기준이이용되고있다. 급성췌장염은초기에경증또는중등도로평가된경우에도중증급성췌장염으로갑자기진행할수있기때문에지속적인중증도평가가필요하다. 4 권고사항급성췌장염의중증도평가는적절한초기치료와향후치료전략의결정에필요하다. -권고등급: B -동의수준: 전적으로동의함 (58%), 대체로동의함 (40%), 일부동의함 (1%), 전적으로동의하지않음 (1%) 2. 임상증상, 징후및임상검사를통한중증도평가 (severity assessment based on clinical symptoms, signs and clinical laboratory tests) 입원시장기부전이동반된경우사망률이높은것으로알려져있다 입원시장기부전이동반된환자들중, 여러장기부전이동반된경우에는사망률이더욱높은것으로알려져있고, 10 장기부전이오래지속될수록사망률이높아, 8,9,12 이를조기에교정하기위한노력이필요하다. 급성췌장염은복부합병증이나주요장기부전을시사하는광범위한임상증상및징후를발현하기때문에, 이러한임상증상및징후만으로는중증도를평가하는데있어서재현성이떨어지는것으로알려져있다. 13 환자의연령은많은연구들 5,10,14-18 에서급성췌장염의중증도와관련이있다고보고하였지만, 이에반하는연구들 도많아중증도를평가하는단일기준으로적용하기에는한계가있다. 서구에서는임상증상및징후이외에신체질량지수 (Body Mass Index; BMI) 30 kg/m 2 이상인비만이중증급성췌장염과관련이있는것으로알려져있다 (Level 2 4). 25,26 하지만, 비만이급성췌장염과관련된사망에는관련이없다는보고도있다. 27 입원후 24시간이내에시행한흉부단순촬영에서확인된흉수가췌장의괴사또는장기부전, 28 높은사망률 17,29 과비례하고, 흉부단순촬영에서의침윤도높은사망률과관련이있다는보고도있다. 17,29,30 C-reactive protein (CRP) 수치는급성췌장염악화를제시하는믿을만한인자로여겨지고있다 여러권고안들 에서도급성췌장염발생 48시간이후측정한 15 mg/dl 이상의혈청 CRP 수치를예후인자로추천하고있다. 이외의다른검사를통해급성췌장염의중증도와연관성을찾으려는시도들이있었다. 입원시혈청 blood urea nitrogen (BUN) 20 mg/dl 과입원 24시간이후 BUN 상승이사망률과연관성을가진다는보고가있었고, 37 입원시 20 와입원 24시간이내 29,38 의혈청 creatinine > 2.0 mg/dl 이높은사망률과관련이있다는보고가있었다. 아울러, 입원 48시간내의혈청 creatinine 상승이췌장의괴사와관련이있다는보고도있다. 39 급성췌장염에서혈당 > 250 mg/dl 인경우높은사망률과관련을가진다는보고도있지만, 20 혈당 > 125 mg/dl 는장기부전이나사망률과는연관성이떨어진다는보고도있다. 40 급성췌장염환자에서혈관내용적의감소로인한적혈구용적률의상승과관련된입원시적혈구용적률 (hematocrit) 44% 이거나입원후 24시간이내에적혈구용적률이감소되지않는경우는췌장의괴사와연관된예측인자로제시되었다. 41 아울러, 입원시적혈구용적률의상승이없는경우괴사성췌장염의발생가능성이매우낮은것으로알려졌다. 41,42 하지만, 다른연구들에서는입

16 이상협외 3 인 16 원시와입원후 24시간의적혈구용적률의상승이중증급성췌장염의예측인자로확인되지는않았다. 38,42 췌장효소활성펩타이드, 특히 trypsinogen activation peptide와 carboxypeptidase activation peptide 측정은급성췌장염의중증도예측에중요한정보를제공하지만, 혈청 CRP 이외에는신속검사가어려워임상적유용성은떨어진다. 36 권고사항임상증상과징후에만근거한중증도평가는신뢰성이떨어지므로단순흉부촬영, 혈청 C-reactive protein (CRP), 혈청 blood urea nitrogen (BUN), 혈청 creatinine 측정등의객관적인임상검사가필요하다. -권고등급: B -동의수준: 전적으로동의함 (45%), 대체로동의함 (49%), 일부동의함 (6%), 전적으로동의하지않음 (1%) 3. 영상검사를통한중증도평가 (severity assessment based on diagnostic imaging) 급성췌장염에서췌장의허혈, 괴사및병변의범위를 평가하기위해조영증강복부전산화단층촬영 (contrast enhanced computed tomography) 이필요하다. 47 조영증강복부전산화단층촬영은괴사성췌장염과부종성췌장염을구별하는데가장유용한검사이다. 47 복부전산화단층촬영에서확인된췌장의괴사는국소및전신합병증과밀접한연관성이있는것으로알려져있어, 복부전산화단층촬영은췌장의괴사가의심되는경우에적절한검사이다. 51 조영증강복부전산화단층촬영은급성췌장염발병 4~10일후시행하면거의 100% 에서췌장괴사의진단이가능하고, 47,52-54 입원초기 ( 입원후 36~48 시간이내 ) 에시행하여도급성췌장염의중증도평가에유용하다. 55,56 Computed tomography severity index (CT severity index) 57 는췌장괴사의유무, 괴사범위및염증변화의범위등을결합하여수치화하였고 (Table 1), 예후와잘연관되어있는것으로받아들여지고있다. CT severity index가 0 2 인경증급성췌장염환자는임상양상이악화되는경우에만복부전산화단층촬영을추가로시행하고, CT severity index 가 3 10 인중등도이상의급성췌장염환자에서는임상상의호전이없는경우에도시행한다 34. 중증도의경과관찰을위한복부전산화단층촬영의시행결정은입원후대략 1주일뒤에권고된다. 36 아울러, 급성췌장염이회복되어퇴원하는경우에도가성낭이나가성동맥류와같은무증상합병증을발견하기위해 Table 1. Computed tomography (CT) grading of severity CT grade (A) Normal pancreas (B) Oedematous pancreatitis (C) B plus mild extrapancreatic changes (D) Severe extrapancreatic changes including one fluid collection (E) Multiple or extensive extrapancreatic collections Necrosis None <One third One third-one half >Half CT severity index = CT grade+necrosis score Modified from the World Association guidelines and based on Balthazar and colleagues Complications 8% 35% 92% Deaths 3% 6% 17%

17 급성췌장염진료권고안 : 급성췌장염의중증도평가 17 Table 2. Ranson criteria for the prediction of severity of acute pancreatitis On admission Age> 55 years (> 70 years) White cell count> 16,000 /mm3 (18,000 /mm 3 ) Lactate dehydrogenase> 350 U/L (> 400 U/L) Aspartate aminotransferase> 250 U/L (same) Glucose> 200 mg/dl (> 220 mg/dl) During initial 48 h Decrease in hematocrit by 10% (same) Blood urea nitrogen increases by> 5 mg/dl (> 2 mg/dl) Calcium< 8 mg/dl(same) PaO2< 60 mmhg(omitted) Base deficit> 4 meq/l (> 6 meq/l) Fluid sequestration>6 L (> 4 L) 복부전산화단층촬영의시행이권고되기도한다. 34 조영증강복부자기공명영상도조영증강복부전산화단층촬영과유사한정도로췌장괴사의유무, 괴사및염증성변화의범위등을평가하는데유용한것으로알려져있다 ,60 하지만, 금속물체를가지고있는경우나응급상황에대처가어려운단점이있다. 권고사항 1. 급성췌장염의중증도에대한평가를위해서는조영증강복부전산화단층촬영의시행이필요하고, 장기부전, 패혈증및임상양상이악화되는경우경과관찰을위해추가시행을고려해야한다. -권고등급: A -동의수준: 전적으로동의함 (74%), 대체로동의함 (23%), 일부동의함 (6%), 전적으로동의하지않음 (1%) 2. 중증도평가를위해 CT severity index 가사용되어야한다. -권고등급: A -동의수준: 전적으로동의함 (47%), 대체로동의함 (48%), 일부동의함 (5%), 전적으로동의하지않음 (1%) Table 3. Glasgow severity scoring system for acute pancreatitis Age> 55 years White cell count> 15,000 /mm 3 PaO2< 60 mmhg Serum lactate dehydrogenase> 600 U/L Serum aspartate aminotransferase> 200 U/L Serum albumin< 3.2 g/dl Serum calcium< 8m g/dl Serum glucose> 180 mg/dl Serum urea> 45 mg/dl 4. 중증도판정기준을이용한평가 (severity assessment based on scoring system) 중증도판정기준을이용한평가에대한권고안을논하기전에현재이용되고있는중증도판정기준들을살펴보고자한다. Ranson 지표는 1974년 Ranson 이발표한임상지표법으로다변수평가법중가장많이알려진것이다. 43개의임상, 생화학지표를분석한결과 11개의항목이예후와관련있음이밝혀졌다. 61 입원시에 5개항목, 입원후 48시간이내에 6개항목을측정하여 3가지이상관찰되는경우중증췌장염으로정의하였다 (Table 2). Glasgow 지표는 Imrie 등이개발한알코올과담석췌장염에모두사용할수있는 Ranson 지표와유사한다변수평가법으로, Ranson 지표중 3개지표를삭제하고알부민을첨가하여총 9개의지표로단순화하였다 (Table 3). 62 APACHE (Acute Physiology and Chronic Health Evaluation) II 지표는특정질환에대한임상평가가아니라중환자실에서이용되어온지표로 12가지의생리적인측정치와나이, 5개의장기에기초한만성건강상태를평가하고이를점수화하여전체점수를합산하는방법으로산출된다 (Table 4). 63 APACHE II 지표는입원수시간내에급성췌장염의중증도를판정할수있고수시로반복측정할수있어진행여부를평가할수있다는장점이있다. 비만이중증급성췌장염의발병과관련이있고사망의독립적인예측인자로인식되면서 APACHE II 지표에신체질량지수를더하여새로운 APACHE-O 지표가만들어졌다. 64 즉신체질량지수가 인경우 1점, 30 이상인경우 2점으로계산한다. 신일본중증도지표 (new Japanese severity scoring system) 는 9개의예후인자와조영증강복부전산화단층촬영등급이중증도평가에이용된다 (Table 5). 65 BISAP (Bedside index for severity in acute pan-

18 이상협외 3 인 18 Table 4. APACHE (acute physiology and chronic health evaluation) II scoring system Physiological parameter Temperature, rectum ( ) Mean arterial pressure (mmhg) Heart rate (n/min) Respiration rate (n/min) Oxygenation (mmhg) a. FiO 2 > 0.5, A-a DO 2 b. FiO 2 < 0.5, PO 2 Arterial ph Serum sodium (mmol/l) Serum potassium (mmol/l) Serum creatinine (mg/dl) (Duplication in acute renal failure) Hematocrit (%) White cell blood count ( x 10 3 /mm) 15 minus Glasgow coma scale score < 200 > < In these 12 parameters must be added the age (years) [< 44:0, 45-54:2, 55-64:3, 65-74:5, > 75:6] and the coexisting systemic disease (severe organ failure or immunosuppression: 5; emergency operation: 5; elective operation: 2) < 55 < < 2.5 < 20 < 1 creatitis) 지표 (Table 6) 66 는입원 24시간동안 BUN > 25 mg/dl, impaired mental status, Systemic Inflammatory Response Syndrome (SIRS), age > 60 years, pleural effusion 5개항목을갖고각각 1점을주어점수가높아짐에따라사망률이높아짐을보고하였다. 급성췌장염은복부합병증이나주요장기부전을시사하는광범위한임상증상및징후를발현하는데, 이러한임상증상및징후는중증도판정기준 (severity scoring system) 의요인으로도이용되어오고있다. 62,67-69 Ranson 지표는해당항목이 3개미만인경우사망률이 0~3%, 20,29,70 3~5개인경우사망률이 11 15% 이고, 20,29,70 6개이상인경우에는사망률이 40% 에달하는것으로알려져있다. 20 Ranson 지표를이용한평가는 48시간이소요되지만, 급성췌장염의악화를 70 80% 정도예측할수있는것으로알려져있다. 61,71,72 하지만, 최근 Ranson 지표에대한연구 110개를종합하여평가한결과에서는발병초기에급성췌장염의중증도를예측하는정도가매우낮은것으로나타났다. 73 APACHE II 지표는급성췌장염의중증도평가에유용한지표로알려져있다. 입원시및입원직후 72시간동안의높은 APACHE-II 지표는높은사망률과연관이있는것으로알려져있다 (< 4%, APACHE-II < 8; 11 18%, APACHE-II > 8). 9,10,19,20,74,75 입원후첫 24시간동안의 APACHE-II 지표를이용한평가는 48시간이후 Ranson 지표를이용한평가와비교하여 중증급성췌장염을예측하는데있어유사한예측도를가진다. 21 이러한이유로, APACHE-II 지표는입원후첫 24 시간동안유용하게이용될수있고, 매일중증도를평가하는데유용한것으로알려져있다. 21 신일본지표의유용성에대한평가에서중증도평가에신일본지표가 Ranson 지표와 APACHE II 만큼유용하다는보고가있었다. 74 이후최근발표된연구에서도 BISAP 지표는사망률과유의한상관관계를보였고, APACHE II 지표, Computed tomography severity index (CTSI) 와유사한정확도를보이는간단하면서도유용한검사로보고했다. 75,76 하지만, 최근 Ranson 지표, Glasgow 지표, APACHE II 지표, 신일본지표, BISAP 지표등을포함한여러중증도판정기준들의정확도를비교한연구에서는모든중증도판정기준들이어느정도유용하고, 유용성에서우열을가리기어려운것으로보고하였다. 77 권고사항췌장암의중증도평가를위해서는중증도판정기준을이용하여야하고, APACHE II 지표등을포함한여러여러중증도판정기준들이유용하게이용될수있다. -권고등급: B -동의수준: 전적으로동의함 (25%), 대체로동의함 (61%), 일부동의함 (14%), 전적으로동의하지않음 (0%) 5. 전원기준 (transfer criteria)

19 급성췌장염진료권고안 : 급성췌장염의중증도평가 19 Table 5. The new japanese severity scoring system of acute pancreatitis (2008) Prognostic factors (1 point for each factor) 1. Base Excess 3 meq/l or shock (systolic blood pressure< 80mmHg) 2. PaO2 60 mmhg (room air) or respiratory failure (respirator management is needed) 3. BUN 40 mg/dl (or Cr 2.0 mg/dl) or oliguria (daily urine output< 400 ml even after IV fluid resuscitation) 4. LDH 2 times of upper limit of normal 5. Platelet count 100,000 /mm 3 6. Serum Ca 7.5 mg/dl 7. CRP 15 mg/dl 8. Number of positive measures in SIRS criteria 3 9. Age 70 years CT Grade by CECT 1. Extrapancreatic progression of inflammation Anterior pararenal space Root of mesocolon Beyond lower pole of kidney 2. Hypoenhanced lesion of the pancreas The pancreas is conveniently divided into three segments (head, body, and tail). Localized in each segment or only surrounding the pancreas Covers 2 segments Occupies entire 2 segments or more 1+ 2 = Total scores Total score = 0 or 1 Total score = 2 Total score = 3 or more 0 point 1 point 2 points 0 point 1 point 2 points Grade 1 Grade 2 Grade 3 Assessment of severity (1) If prognostic factors are scoredas 3 points or more, or (2) If CT Grade is judged as Grade 2 or more, the severity grading is evaluated to be as "severe". Measures in SIRS diagnostic criteria: (1) Temperature> 38 or < 36, (2) Heart rate> 90 beats/min, (3) Respiratory rate> 20 breaths/min or PaCO 2< 32 torr, (4) WBC> 12,000 cells/mm 3, < 4,000cells/mm 3, or 10% immature (band) forms Table 6. BISAP (bedside index for severity in acute pancreatitis) scoring system BUN> 25 mg/dl Impaired mental status (Glasgow Coma Scale Score< 15) SIRS SIRS is defined as two or more of the following: (1) Temperature of< 36 or > 38 (2) Respiratory rate> 20 breaths/min or PaCO2< 32 mmhg (3) Pulse>90 beats/min (4) WBC< 4,000 or> 12,000 cells/mm 3 or> 10% immature bands Age> 60 years Pleural effusion detected on imaging One point is assigned for each variable within 24 h of presentation and added for a composite score of 0-5. 이전부터여러권고안들은 34,69,78 APACHE II 지표 > 8 을중증급성췌장염으로분류하여적절한치료방침수립에이용할것을권고하고있었다. 이외에, Santorini consensus conference(1999) 35 는 BMI > 30 kg/m 2 이상 의비만, 흉수가관찰되는경우, APACHE II 지표 6, APACHE-O 지표 6 및혈청 CRP 수치 15 mg/dl 이상인경우중증급성췌장염으로분류하여적절한치료가가능한병원으로전원을권고하였다. 미국권고안 79 은

20 이상협외 3 인 20 장기부전이있는경우, 적극적인수액요법이필요한경우, 특히세심한수액요법이필요한심부전이있는고령의환자, 기관지삽관을포함한인공환기집중치료가필요할것으로예상되는환자는중환자실 (ICU) 에서치료가가능한병원으로신속한전원하고, 비만 ( 신체질량지수 > 30 kg/m2), 핍뇨 (urine output < 50 ml/h), 빈맥 (pulse > 120 beats/min), 뇌병증, 마약성진통제의요구량이증가하는경우에는전원에대비하여주위깊게관찰할것을제안하였다. 79 권고사항중증급성췌장염으로평가된환자는집중치료실이있고, 내시경중재시술, 영상중재시술및수술처치가가능한병원으로전원해야한다. -권고등급: B -동의수준: 전적으로동의함 (55%), 대체로동의함 (40%), 일부동의함 (3%), 전적으로동의하지않음 (2%) 결론 우리나라의적합한급성췌장염의중증도평가에대한권고안으로본고에제시된내용은결론을내리기에는자료나토의등준비가충분치않지만, 향후보다진전된결론에도달하기위한하나의과정으로생각한다. 아울러, 환자를진료하는임상의사간또의료기관간급성췌장염의중증도평가를표준화하여급성췌장염의임상연구활성화하고적절한치료를제공하는계기가될수있기를기대한다. 국문초록 급성췌장염초기의중증도정도의평가는적절한초기치료와중증급성췌장염에대응할수있는의료시설로환자의전원을결정하는데중요한역할을하며, 초기치료이후에도지속적인중증도평가는치료방침결정에중요하다. 현재급성췌장염중증도평가에대한진료지침은일본, 이탈리아, 미국, 그리고영국등여러나라에서개발되어사용되고있으며재평가되고있다. 중증급성췌장염환자는전문의료센터또는적절한인력과시설을갖춘 중환자실이있는의료기관으로전원되어적절한치료를받아야한다. 이번에제안된대한췌담도학회의진료지침을통해우리나라에서중증급성췌장염환자에대한적절한치료뿐만아니라, 이에대한임상연구활성화의계기가마련되기를기대한다. 색인단어 : 급성췌장염, 중증도, 진료지침 참고문헌 1. Russo MW, Wei JT, Thiny MT, et al. Digestive and liver diseases statistics, Gastroenterology 2004;126: Uhl W, Warshaw A, Imrie C, et al. IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology: official journal of the International Association of Pancreatology 2002;2: Pandol SJ, Saluja AK, Imrie CW, Banks PA. Acute pancreatitis: bench to the bedside. Gastroenterology 2007;132: Hirota M, Takada T, Kawarada Y, et al. JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006;13: Lankisch PG, Pflichthofer D, Lehnick D. No strict correlation between necrosis and organ failure in acute pancreatitis. Pancreas 2000;20: Polyzogopoulou E, Bikas C, Danikas D, Koutras A, Kalfarentzos F, Gogos CA. Baseline hypoxemia as a prognostic marker for pulmonary complications and outcome in patients with acute pancreatitis. Dig Dis Sci 2004;49: Isenmann R, Rau B, Beger HG. Early severe acute pancreatitis: characteristics of a new subgroup. Pancreas 2001;22: Buter A, Imrie CW, Carter CR, Evans S, McKay CJ. Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. Br J Surg 2002;89: Johnson CD, Abu-Hilal M. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Gut 2004;53: Perez A, Whang EE, Brooks DC, et al. Is severity of necrotizing pancreatitis increased in extended necrosis and infected necrosis? Pancreas 2002;25: McKay CJ, Buter A. Natural history of organ failure in acute pancreatitis. Pancreatology 2003;3: Flint R, Windsor JA. Early physiological response to intensive care as a clinically relevant approach to predicting

21 급성췌장염진료권고안 : 급성췌장염의중증도평가 21 the outcome in severe acute pancreatitis. Arch Surg 2004;139: United Kingdom guidelines for the management of acute pancreatitis. British Society of Gastroenterology. Gut 1998;42 Suppl 2:S Connor S, Ghaneh P, Raraty M, et al. Increasing age and APACHE II scores are the main determinants of outcome from pancreatic necrosectomy. Br J Surg 2003;90: Halonen KI, Leppaniemi AK, Puolakkainen PA, et al. Severe acute pancreatitis: prognostic factors in 270 consecutive patients. Pancreas 2000;21: Halonen KI, Leppaniemi AK, Lundin JE, Puolakkainen PA, Kemppainen EA, Haapiainen RK. Predicting fatal outcome in the early phase of severe acute pancreatitis by using novel prognostic models. Pancreatology 2003;3: Talamini G, Bassi C, Falconi M, et al. Risk of death from acute pancreatitis - Role of early, simple ''routine'' data. Int J Pancreatol 1996;19: Malangoni MA, Martin AS. Outcome of severe acute pancreatitis. Am J Surg 2005;189: Rahman SH, Ibrahim K, Larvin M, Kingsnorth A, McMahon MJ. Association of antioxidant enzyme gene polymorphisms and glutathione status with severe acute pancreatitis. Gastroenterology 2004;126: Blum T, Maisonneuve P, Lowenfels AB, Lankisch PG. Fatal outcome in acute pancreatitis: its occurrence and early prediction. Pancreatology 2001;1: Chatzicostas C, Roussomoustakaki M, Vlachonikolis IG, et al. Comparison of Ranson, APACHE II and APACHE III scoring systems in acute pancreatitis. Pancreas 2002;25: Modrau IS, Floyd AK, Thorlacius-Ussing O. The clinical value of procalcitonin in early assessment of acute pancreatitis. Am J Gastroenterol 2005;100: Gullo L, Migliori M, Olah A, et al. Acute pancreatitis in five European countries: etiology and mortality. Pancreas 2002;24: Kim JE, Hwang JH, Lee SH, et al. The clinical outcome of elderly patients with acute pancreatitis is not different in spite of the different etiologies and severity. Arch Gerontol Geriatr 2012;54: Funnell IC, Bornman PC, Weakley SP, Terblanche J, Marks IN. Obesity: an important prognostic factor in acute pancreatitis. Br J Surg 1993;80: Martinez J, Sanchez-Paya J, Palazon JM, Aparicio JR, Pico A, Perez-Mateo M. Obesity: a prognostic factor of severity in acute pancreatitis. Pancreas 1999;19: Martinez J, Sanchez-Paya J, Palazon JM, Suazo-Barahona J, Robles-Diaz G, Perez-Mateo M. Is obesity a risk factor in acute pancreatitis? A meta-analysis. Pancreatology 2004;4: Heller SJ, Noordhoek E, Tenner SM, et al. Pleural effusion as a predictor of severity in acute pancreatitis. Pancreas 1997;15: Talamini G, Uomo G, Pezzilli R, et al. Serum creatinine and chest radiographs in the early assessment of acute pancreatitis. Am J Surg 1999;177: Lankisch PG, Droge M, Becher R. Pulmonary infiltrations. Sign of severe acute pancreatitis. Pancreatology 1996;19: Viedma JA, Perez-Mateo M, Agullo J, Dominguez JE, Carballo F. Inflammatory response in the early prediction of severity in human acute pancreatitis. Gut 1994;35: Pezzilli R, Billi P, Miniero R, et al. Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein. Dig Dis Sci 1995;40: Uchikov PA, Sirakova IP, Murdjeva MA, Uchikov AP. Changes in plasma levels of acute phase proteins in pancreatitis. Folia med(plovdiv) 2000;42: Toouli J, Brooke-Smith M, Bassi C, et al. Guidelines for the management of acute pancreatitis. J Gastroenterol Hepatol 2002;17(suppl);S Dervenis C, Johnson CD, Bassi C, et al. Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference. Pancreatology 1999;25: UK guidelines for the management of acute pancreatitis. Gut 2005;54(Suppl 3);iii1-iii9 37. Wu BU, Bakker OJ, Papachristou GI, et al. Blood urea nitrogen in the early assessment of acute pancreatitis: an international validation study. Arch Intern Med 2011;171: Talamini G, Bassi C, Falconi M, et al. Risk of death from acute pancreatitis. Role of early, simple "routine" data. Pancreatology 1996;19: Muddana V, Whitcomb DC, Khalid A, Slivka A, Papachristou GI. Elevated serum creatinine as a marker of pancreatic necrosis in acute pancreatitis. Am J Gastroenterol 2009;104: Lankisch PG, Blum T, Bruns A, et al. Has blood glucose level measured on admission to hospital in a patient with acute pancreatitis any prognostic value? Pancreatology 2001;1:

22 이상협외 3 인 Brown A, Orav J, Banks PA. Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis. Pancreas 2000;20: Lankisch PG, Mahlke R, Blum T, et al. Hemoconcentration: an early marker of severe and/or necrotizing pancreatitis? A critical appraisal. Am J Gastroenterol 2001;96: Appelros S, Petersson U, Toh S, Johnson C, Borgstrom A. Activation peptide of carboxypeptidase B and anionic trypsinogen as early predictors of the severity of acute pancreatitis. Br J Surg 2001;88: Tenner S, Fernandez-del Castillo C, Warshaw A, et al. Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis. Pancreatology 1997;21: Neoptolemos JP, Kemppainen EA, Mayer JM, et al. Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study. Lancet 2000;355: Rau B, Cebulla M, Uhl W, Schoenberg MH, Beger HG. The clinical value of human pancreas-specific protein procarboxypeptidase B as an indicator of necrosis in acute pancreatitis: comparison to CRP and LDH. Pancreas 1998;17: Larvin M, Chalmers AG, McMahon MJ. Dynamic contrast enhanced computed tomography: a precise technique for identifying and localising pancreatic necrosis. BMJ 1990;300: Buchler MW, Gloor B, Muller CA, Friess H, Seiler CA, Uhl W. Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann Surg 2000;232: Uhl W, Roggo A, Kirschstein T, et al. Influence of contrast-enhanced computed tomography on course and outcome in patients with acute pancreatitis. Pancreas 2002;24: Isenmann R, Rau B, Beger HG. Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis. Br J Surg 1999;86: Takeda K, Yokoe M, Takada T, et al. Assessment of severity of acute pancreatitis according to new prognostic factors and CT grading. J Hepatolbiliary Pancreat Sci 2010;17: Vesentini S, Bassi C, Talamini G, Cavallini G, Campedelli A, Pederzoli P. Prospective comparison of C-reactive protein level, Ranson score and contrast-enhanced computed tomography in the prediction of septic complications of acute pancreatitis. Br J Surg 1993;80: Kemppainen E, Sainio V, Haapiainen R, Kivisaari L, Kivilaakso E, Puolakkainen P. Early localization of necrosis by contrast-enhanced computed tomography can predict outcome in severe acute pancreatitis. Br J Surg 1996;83: Clavien PA, Hauser H, Meyer P, Rohner A. Rapid-bolus contrast-enhanced dynamic computed tomography in acute pancreatitis: a prospective study. Br J Surg 1991;78: Clavien PA, Hauser H, Meyer P, et al. Value of contrast-enhanced computerized tomography in the early diagnosis and prognosis of acute pancreatitis. A prospective study of 202 patients. Am J Surg 1988;155: Rotman N, Chevret S, Pezet D, et al. Prognostic value of early computed tomographic scans in severe acute pancreatitis. French Association for Surgical Research. J Am Coll Surg 1994;179: Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology 1990;174: Hirota M, Kimura Y, Ishiko T, Beppu T, Yamashita Y, Ogawa M. Visualization of the heterogeneous internal structure of so-called "pancreatic necrosis" by magnetic resonance imaging in acute necrotizing pancreatitis. Pancreas 2002;25: Ward J, Chalmers AG, Guthrie AJ, Larvin M, Robinson PJ. T2-weighted and dynamic enhanced MRI in acute pancreatitis: comparison with contrast enhanced CT. Clin Radiol 1997;52: Lecesne R, Taourel P, Bret PM, Atri M, Reinhold C. Acute pancreatitis: interobserver agreement and correlation of CT and MR cholangiopancreatography with outcome. Radiology 1999;211: Ranson JH, Rifkind KM, Roses DF, Fink SD, Eng K, Spencer FC. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecol Obstet 1974;139: Imrie CW, Benjamin IS, Ferguson JC, et al. A single-centre double-blind trial of Trasylol therapy in primary acute pancreatitis. Br J Surg 1978;65: Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13: Johnson CD, Toh SK, Campbell MJ. Combination of APACHE-II score and an obesity score(apache-o) for the prediction of severe acute pancreatitis. Pancreatology 2004;4:1-6.

23 급성췌장염진료권고안 : 급성췌장염의중증도평가 Ueda T, Takeyama Y, Yasuda T, et al. Utility of the new Japanese severity score and indications for special therapies in acute pancreatitis. J Gastroenterol 2009;44: Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut 2008;57: Ogawa M, Hirota M, Hayakawa T, et al. Development and use of a new staging system for severe acute pancreatitis based on a nationwide survey in Japan. Pancreas 2002;25: Bank S, Wise L, Gersten M. Risk factors in acute pancreatitis. Am J Gastroenterol 1983;78: Bradley EL, 3rd. A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Ga, September 11 through 13, Arch Surg 1993;128: Lankisch PG, Struckmann K, Assmus C, Lehnick D, Maisonneuve P, Lowenfels AB. Do we need a computed tomography examination in all patients with acute pancreatitis within 72 h after admission to hospital for the detection of pancreatic necrosis? Scand J Gastroenterol 2001;36: Blamey SL, Imrie CW, O'Neill J, Gilmour WH, Carter DC. Prognostic factors in acute pancreatitis. Gut 1984;25: Leese T, Shaw D. Comparison of three Glasgow multifactor prognostic scoring systems in acute pancreatitis. Br J Surg 1988;75: De Bernardinis M, Violi V, Roncoroni L, Boselli AS, Giunta A, Peracchia A. Discriminant power and information content of Ranson's prognostic signs in acute pancreatitis: a meta-analytic study. Crit Care Med 1999;27: S M, K T, M K. Annual report 2005, Committee of Intractable Disease of the Pancreas Japanese Ministry of Health, Labor and Welfare 2005:32-38(in Japanese). 75. Papachristou GI, Muddana V, Yadav D, et al. Comparison of BISAP, Ranson's, APACHE-II, and CTSI scores in predicting organ failure, complications, and mortality in acute pancreatitis. Am J Gastroenterol 2010;105: ; quiz Singh VK, Wu BU, BollenTL, et al. A prospective evaluation of the bedside index for severity in acute pancreatitis score in assessing mortality and intermediate markers of severity in acute pancreatitis. Am J Gastroenterol 2009;104: Mounzer R, Langmead CJ, Wu BU, et al. Comparison of existing clinical scoring systems to predict persistent organ failure in patients with acute pancreatitis. Gastroenterology 2012;142: ; quiz e Pezzilli R, Zerbi A, Di Carlo V, Bassi C, Delle Fave GF. Practical guidelines for acute pancreatitis. Pancreatology 2010;10: Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101:

24 REVIEW ARTICLE pissn eissn THE KOREAN JOURNAL OF PANCREAS AND BILIARY TRACT 급성췌장염진료권고안 : 급성췌장염의초기치료 이태훈 1, 한정호 2, 박상흠 1 1 순천향대학교의과대학천안병원내과, 2 충북대학교의과대학내과 Clinical Practice Guideline for Acute Pancreatitis: Initial Management of Acute Pancreatitis Tae Hoon Lee 1, Joung-Ho Han 2, Sang-Heum Park 1 1 Division of Gastroenterology, Department of Internal Medicine, Soon Chun Hyang University School of Medicine, Cheonan Hospital, Cheonan, Republic of Korea 2 Chungbuk National University College of Medicine, Cheongju, Republic of Korea Initial intensive management of acute pancreatitis is important in reducing the mortality and complications associated with this condition. Nevertheless, the current domestic standard guidelines do not include protocols for the initial management of acute pancreatitis. We used the guidelines currently enacted in Europe, America, and Japan to prepare guidelines for initial management of acute pancreatitis. We recommend an initial treatment that consists of conservative management including fasting and fluid therapy, hyperalimentation, the use of prophylactic antibiotics, and inhibition of pancreatic enzymes including protease inhibitors. Key words: acute pancreatitis, initial management 서론 1) 급성췌장염은정확한진단과함께중증도를예측하여초기집중치료를요하는환자군을선별하여적절한치료를시행하는것이췌장염에의한합병증발생및사망률을감소시키는데중요하다. 그러나아직국내에서는이러한치료지침에대한구체적인기준이마련되어있지않은실정이다. 현재까지발표된영국, 이태리등의유럽가이드라인과미국, 일본의가이드라인을근간으로급성췌장염의초기치료에대한지 Correspongding author. 이태훈순천향대학교의과대학천안병원소화기내과학교실충남천안시동남구순천향 6길 31 ( ) Tel: Fax: [email protected]/ [email protected] 침을살펴보면 1) 금식및적절한수액치료, 2) 기타진통제를포함한보존적치료, 3) 경장관영양법, 4) 합병증을줄이기위한항생제및 protease inhibitor 등의사용으로분류해볼수있다. 1-6 따라서, 이를근간으로급성췌장염의초기치료로서보존적치료를포함한수액치료, 경장관영양법및방법, 예방적항생제의사용, protease inhibitor 를포함한췌장효소억제재의사용순서로나누어근거중심으로알아보고이에대한초기치료의권고사항을정리하고자한다. 본론 1. 수액요법을포함한초기보존적치료급성췌장염자체를호전시키는방법은아직제시된바없으며주로보존적치료와합병증에대한처치가치료의 24

25 급성췌장염진료권고안 : 급성췌장염의초기치료 25 근간으로환자를금식시키고적절한수액공급을조기에실시하는것이가장중요하다. 1) 수액요법급성췌장염환자에서수액량의부족을교정하고기본적인수액필요량을유지하기위해서는적절한정맥내수액공급이즉각적으로이루어져야한다. 초기수액공급의기준은심혈관및신기능유지를목적으로평균혈압 65 mmhg 이상, 소변량 > 0.5~1 ml/kg/hr 를유지할것을권고한다. 1-6 그러나, 모든췌장염환자에서 4 L 이상의과도한수액공급이필요하지는않다. 급성췌장염에서는혈관투과성의증가와 colloid 삼투압의감소로인해췌장주위, 후복막강뿐아니라복강, 흉강등으로세포외액의누출이발생해상당한순환혈장량의손실이유발된다. 저혈량증 (hypovolemia) 은췌장의미세순환 (microcirculation) 을감소시켜괴사성췌장염발생의주요원인이된다. 따라서, 심혈관장애를안정화하고췌장의미세순환을증가시키기위해손실된수액에대한즉각적인공급이필요하다. 또한, 적절한수액공급의지표로활력징후, 소변량및헤마토크릿의감소정도 ( 입원후첫 12시간, 24시간 ) 를적어도매 4~6시간간격으로측정해야한다. 일본지침의경우첫 24시간내에소변량등을지표로 60~160 ml/kg/day 를초기에공급하고이중 1/2~1/3 을첫 6시간이내에투여할것을권고하기도한다. 일반적으로중심정맥압측정은필요하지않으나중증의췌장염에서는적절한 volume 상태파악을위해필요하고, 폐동맥쐐기압 (pulmonary wedge pressure), 동맥가스혈분석, 전해질검사등을시행해야한다. 1-6 대부분의시험적연구에서초기의적극적인수액공급및산소공급은췌장괴사를최소화하고생존율을증가시킨다고보고하고있다. 7-9 그러나최근몇몇연구결과에서는초기 24시간이내에 4 L 이상의과도한수액공급이모든환자에서필요하지는않으며초기에과도한수액공급으로인한혈액희석 (hemodilution) 으로호흡기합병증이증가하거나패혈증및사망률빈도가높아진다는보고도있다 이러한연구결과들은합병증의수가너무적어신뢰도가떨어지고경증의환자에서상대적으로적은수액공급에도좋은결과를보여주는선택적오류가있어향후좀더세분화한광범위전향적비교연구가필요하다. 지속적인저산소혈증이나저혈압, 신부전등의장기부전이발생하였거나초기수액치료에반응이없는경우, 혹은중증의기저심폐질환이있는고령환자에서는즉시중환자실에서모니터링하면서집중적인치료를시행해야한다. 그리고 BMI > 30, 시간당소변량 < 50 ml, 분당심박수 > 120회, 뇌증, 극심한통증으로마약성진통제의필요증가등의경우역시당장중환자실로전실하지않더라도경과에주의하며이에준한집중치료가필요하다 ) 산소공급산소공급은첫 24~48 시간동안투여를권고하는데, 특히통증등으로마약성진통제 (narcotic agent) 를사용하는경우에는초기에침상에서산소포화도모니터링을하면서공급한다. 산소농도는적어도 95% 이상유지되어야하며 95% 이하인경우동맥가스혈분석을시행한다 ) 통증조절급성췌장염과연관된통증은지속적이고심해불안감을야기하고임상경과에악영향을미칠수있으므로마약성진통제등을이용한복통의완화는치료초기에매우중요하다. 현재까지는어떤특정한형태의투약에대한명확한이점이보고된바없으나일부연구에서 non-narcotic analgesic buprenorphine이 procaine보다우수하여오디괄약근수축과같은악영향을미치지않고 pethidine(meperidine hydrochloride; Demerol) 과비슷한진통효과가있다고한다 진통제투약의빈도나양은경험있는의사에의해모니터링되어야하며동시에침상에서산소포화도모니터링을시행해야한다. 또한복통이심할경우환자주도통증조절 (patient-controlled analgesia) 을시행해볼수있다. 4) 경비위배액경비위배액 (nasogastric drainage) 은경증의급성췌장염에서는필요하지않으나마비성장폐쇄 (paralytic ileus) 나잦은구토등이있는경우필요할수있다. 그러나급성췌장염환자에서경비위배액이췌장의안정화에유용하다는뚜렷한연구결과는없다. 경증및중등도췌장염의 RCT 연구에서위배액은통증경감이나입원기간단축등의임상경과에의미있는영향을주지못했다. 오히려통증이나구역감을증가시킨다는보고들도있다. 따라서, 모든췌장염에서경비배액관삽입은권고되지않으며췌장염으로인한마비성장폐쇄나잦은구토가있는경우삽입을고려해야한다. 1-6

26 이태훈외 2 명 26 5) 제산제및기타일반적으로 H2-blocker 나 PPI (proton pump inhibitor) 는급성췌장염환자에서급성위점막병변 (acute gastric mucosal lesion) 이나출혈성궤양을동반한경우를제외하고는필요하지않다. 1-6 PPI 사용효과에대한무작위비교연구는아직없고이에대한지침역시아직보고된바없으나스트레스성궤양이나급성위점막병변이발생한급성췌장염의경우사용을고려한다. 한문헌고찰에서는 cimetidine 이급성췌장염과연관된합병증의빈도를증가시키는경향이있고통증기간을증가시킬수도있다고보고하고있다. 16 그렇지만현재까지 cimetidine 이나 H2-blocker, PPI 등이급성췌장염의임상경과를호전혹은악화시킬수있다는임상적근거는부족하다. 권고사항 1. 급성췌장염치료의근간은금식과적절한수액공급으로초기에수액양의부족을교정하고기본적인수액필요량을유지하기위해적절한정맥내수액공급을즉각적으로시행해야한다. 초기수액공급양은심혈관및신기능유지를목적으로평균혈압 65 mmhg 이상, 소변량 > 0.5~1 ml/kg/hr 을유지할수있도록공급해야한다 (60~160 ml/kg/day). - 권고등급 : A - 동의수준 : 전적으로동의함 (72%), 대체로동의함 (27%), 일부동의함 (0%), 전적으로동의하지않음 (1%) 2. 급성췌장염과연관된통증은지속적이고심해통증조절은급성췌장염치료에매우중요하다. - 권고등급 : A - 동의수준 : 전적으로동의함 (73%), 대체로동의함 (25%), 일부동의함 (1%), 전적으로동의하지않음 (1%) 3. 경비위배액은경증의급성췌장염에서는필요하지않으나마비성장폐쇄나잦은구토등이있을때필요하다. - 권고등급 : B - 동의수준 : 전적으로동의함 (39%), 대체로동의함 (49%), 일부동의함 (11%), 전적으로동의하지않음 (1%) 4. 급성췌장염에서 H2-blocker 나 PPI는급성위점막병변이나출혈성궤양을동반한경우투여할수있다. - 권고등급 : C - 동의수준 : 전적으로동의함 (24%), 대체로동의함 (66%), 일부동의함 (10%), 전적으로동의하지않음 (0%) 2. 영양지원경증의급성췌장염에서자연적인식이진행은대부분 3~7일내가능하므로비경구영양법이나경장관영양법 (enteral nutrition) 이필요하지는않다. 일반적으로경증의췌장염에서환자는통증이없어지면짧은기간금식후경구식이가가능하고통증이없으면가능한빨리경구식이를진행하는것이좋다. 따라서, 경증의췌장염에서는환자가 5~7일이후정상식이를섭취할수있다면경장관영양등은일반적으로필요하지않다. 1-6 경장관영양법은중증의급성췌장염초기에장마비등이없다면조기에시작하는것이경정맥영양법 (intravenous hyperalimentation) 보다우수하다 경장관영양법은염증성반응을제거하고감염빈도나수술빈도를낮추고입원기간을단축해비용도절감할수있다고보고되었다. 그러나, 사망률이나감염외다른합병증의발생빈도에는별다른차이가없었다. 영양공급은대부분경장관영양만으로가능하나충분한칼로리공급이어렵다면경정맥영양이추가로필요할수있다. 경장관영양법이보다우수하다고판단되는근거는중증의급성췌장염에서장관의장벽기능 (barrier function) 이저하되면박테리아나 endotoxin 의장벽투과성을증가시켜장기부전을일으킬수있는 nitric oxide나 cytokine의생성을촉진시킬수있고, 또한패혈성합병증을일으킬수있는강력한병적장내세균의위내군체형성 (colonization) 빈도를증가시킬수있기때문이다. 경장관영양법은이러한장벽기능을안정화시켜적절한영양공급뿐아니라전신합병증을예방하고이환율및사망률을감소시킬수있다. 또한경정맥영양과관련된감염, 패혈증같은합병증역시피할수있다. 그러나, 최근의메타분석결과를보면경장관영양이우수하다는결과와함께안정성이나효과에서경장관영양법이더우수하다고보기에는자료가충분치않다는의견도있다. 18,25 영양공급로는경비공장배액관 (nasojejunal tube) 이일반적으로추천된다. 일반적으로췌장외분비기능의자극을피하기위해가능한 Treitz ligament 이하로공장배액관 (jejunal tube) 을삽입해영양공급하는것을추천한다. 1-6 그러나, 최근의문헌고찰에따르면경비위배액관을이용한영양공급이공장배액관을이용하는것과비교해안전성이나사망률등에차이가없었다. 26 또한경비위배액관은삽입이비교적쉽고관을유치하기도용이하

27 급성췌장염진료권고안 : 급성췌장염의초기치료 27 다. 26,27 따라서, 경비관삽입은환자상태등에따라선택적으로결정될수있으며향후경비위배액관삽입에대한비교연구가더진행되야한다. 비경구영양법은인체에서췌장의분비기능을유의하게자극하지않고췌장기능에도특별한부작용을일으키지는않는다. 비경구영양법의적응증은비교적단순해지속적인장마비나 complex pancreatic fistulae, abdominal compartment syndrome 등으로인해경장관영양이불가능한경우, 즉경장관영양으로목적한만큼의영양섭취가어려운경우이다. 1-6 경구식이는탄수화물과단백질이충분하고지방이전체에너지섭취의 30% 미만의저지방식이가추천된다. 17 권고사항 1. 경증의급성췌장염에서자연적인식이진행은대부분 3~7일내가능하므로비경구영양법이나경장관영양법이모든환자에서필요하지는않다. - 권고등급 : B - 동의수준 : 전적으로동의함 (43%), 대체로동의함 (51%), 일부동의함 (6%), 전적으로동의하지않음 (0%) 2. 중증의급성췌장염초기에경장관영양법은장마비가없다면조기에시작하는것이경정맥영양법보다우수하고, 경로는일반적으로경비공장배액관을추천한다. - 권고등급 : B - 동의수준 : 전적으로동의함 (21%), 대체로동의함 (59%), 일부동의함 (18%), 전적으로동의하지않음 (2%) 3. 경구식이는탄수화물과단백질이충분하고지방이전체에너지섭취의 30% 미만의저지방식이를추천한다. - 권고등급 : C - 동의수준 : 전적으로동의함 (19%), 대체로동의함 (69%), 일부동의함 (11%), 전적으로동의하지않음 (1%) 3. 예방적항생제투여감염성췌장괴사나패혈증환자에서의사망률은매우높기때문에중증의급성췌장염에서감염성합병증을예방하기위해항생제사용이추천되었다. 일반적으로괴사성췌장염에서발열, 백혈구증가증이나장기부전이동반된경우배양검사나복부 CT 유도하흡입검사등을시행하는동안에예방적으로항생제를사용하는것이합당하다. 이는임상증상이없는괴사성췌장염에서예방적항생제 사용이내성균이나진균감염의기회를제공할수있다는데근거한다. 최근의 RCT 연구결과를보면췌장침투율이좋은 ciprofloxacin, ofloxacin, imipenem, pefloxacine (pefloxacin) 같은항생제를예방적투여시췌장내충분한조직농도를유지할수있어감염성합병증의빈도를낮추고일부연구에서는사망률을감소시킨다는보고가있다. 그렇지만, 사망률이나합병증감소에차이가없었다는보고들도있다. 메타분석에서도췌장침투율이좋은광범위항생제의예방적사용은감염성합병증이나사망률을감소시킨다고보고하였으나역시차이가없다는보고들도있다 따라서, 향후이에대한명확한진단기준에따른광범위한대단위비교연구가필요하다. 또한, 예방적광범위항생제의사용시중증의급성췌장염에서감염성합병증이나사망률을감소시킨다하더라도내성균이나진균감염의위험을증가시키고이로인한사망률을증가시킬수있다는것을고려해야한다 임상연구에서는예방적으로췌장조직침투율이좋은 fluconazole 의사용이중증의급성췌장염에서진균감염의빈도를감소시킨다고보고한바있으나이에대한대조연구는아직보고된바없다. 38,39 결과적으로중증의췌장염에서감염과연관된합병증빈도감소를목적으로조직침투가좋은광범위항생제의예방적투여를해볼수있을것으로보이나, 사망률을감소시키거나 CT로증명된괴사성췌장염에서의생존률을증가시키지는않는것같다. 권고사항 1. 중증의췌장염에서감염과연관된합병증빈도감소를목적으로조직침투가좋은광범위항생제를예방적으로투여해볼수있다. - 권고등급 : B - 동의수준 : 전적으로동의함 (16%), 대체로동의함 (61%), 일부동의함 (21%), 전적으로동의하지않음 (2%) 4. Protease inhibitor 외췌장효소억제재 Protease inhibitor나 anti-secretory, anti-inflammatory agent 등의효과는확실하지않으나, 다량의 protease inhibitor 정맥주입은중증췌장염의초기에합병증빈도를감소시키고사망률을감소시킬수도있다고보고하고있다. 지금까지의초기연구에서 protease inhibitor 나 anti-secretory agent(octreotide), anti-inflammatory

28 이태훈외 2 명 28 agent(lexipafant) 등의유용성이제기되었으나비교연구에서우수한결과를보여주지는못했다 특히급성췌장염에서 protease inhibitor 의유용성은대부분의초기연구에서는실망스런결과를보여주었고일련의 RCT (6 trials of gabexate mesilate and 4 trials of aprotinin) 연구의메타분석에따르면급성췌장염에서 protease inhibitor 의사용이합병증을감소시키나수술적중재술의빈도나사망률을감소시키지는않는다고보고하였다. 43 그러나, 중등도이상의급성췌장염에서는사망률이유의하게감소하였다. 또한, 고용량 gabexate mesilate(2400 mg/day) 의지속정맥주입이장기부전을동반한중증췌장염에서합병증과사망률을감소시켰다는보고도있다. 44 췌장효소분비를억제하는작용이있는 somatostatin 이나이와유사한 octreotide 역시급성췌장염초기에사용하면췌장염에의한합병증이나사망률을감소시킬수있다는연구보고도있지만상반된보고도있다. 이러한연구에대한메타분석에서는 somatostatin 이나 octreotide 같은약물이급성췌장염에서사망률을감소시킬수있다고하였다. 45 일본이나이탈리아가이드라인에서는중등도이상의췌장염초기에췌장효소억제재나 protease inhibitor 의정맥주입치료를권고하고있고, 특히일본의경우 gabexate mesilate, nafamostat mesilate, ulinastatin 등의제재에대해중등도에따른구체적인사용지침을제시하고있다. 2,4,46 그러나여전히영국, 미국등의가이드라인에서는그효과에대한의문을제기하고있고현재치료지침으로인정하고있지않다. 5,6 따라서, 향후지역, 인종및중등도에따른국내외대단위비교연구가필요할것으로생각된다. 권고사항 1. 중증의췌장염환자에서초기합병증빈도나사망률감소를목적으로다량의 protease inhibitor나 somatostatin, octreotide 를투여해볼수있다. - 권고등급 : C - 동의수준 : 전적으로동의함 (7%), 대체로동의함 (39%), 일부동의함 (48%), 전적으로동의하지않음 (7%) 결론 급성췌장염의초기치료에대한권고사항을요약하면 다음과같다. 먼저금식하면서초기에적절한수액치료가적극적으로이루어져야하며통증조절역시초기에적극적으로시행한다. 경장관영양법은중증의급성췌장염에서조기에시작할것을추천하나일반적으로 3~7일내식이가가능한경증췌장염에서는필요하지않다. 예방적항생제투여나 protease inhibitor 및췌장효소억제재는중증췌장염에서합병증이나사망률감소목적으로투여해볼수있을것으로생각된다. 그러나, 지역및인종에따른차이가있고연구결과마다일치하지않으므로향후국내실정에맞는전향적인대규모연구가필요하다. 국문초록 급성췌장염에서초기집중치료는췌장염에의한합병증발생및사망률을감소시키는데중요하다. 그러나아직국내에서는이러한초기치료지침에대한기준이마련되어있지않아현재까지발표된영국, 이태리등의유럽가이드라인과미국및일본등의가이드라인을근간으로급성췌장염초기치료에대한권고안을마련하고자한다. 급성췌장염의초기치료의기본은금식등보존적치료를포함한수액치료, 경장관영양법, 예방적항생제의사용, protease inhibitor 를포함한췌장효소억제재의사용으로권고한다. 색인단어 : 급성췌장염, 초기치료 참고문헌 1. Uomo G, Pezzilli R, Cavallini G. Management of acute pancreatitis in clinical practice. ProInf AISP Study Group: Progetto Informatizzato Pancreatite Acuta-Associazione Italianna Studio Pancreas. Ital J Gastroenterol Hepatol 1993;31: Pezzilli R, Zerbi A, Di Carlo V, et al. Working Group of the Italian Association for the Study of the Pancreas on Acute Pancreatitis. Pancreatology 2010;10: Banks PA. Practice guidelines in acute pancreatitis. Am J Gastroenterol 1997;92: Hirota M, Takada T, Kitamura N, et al. Fundamental and intensive care of acute pancreatitis. J Hepatobiliary Pancreat Sci 2010;17: Banks PA, Freeman ML, and the Practice Parameters Committee of the American College of Gastroenterology.

29 급성췌장염진료권고안 : 급성췌장염의초기치료 29 Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101: UK Working Party on Acute Pancreatitis. UK guidelines for the management of acute pancreatitis. Gut 2005;54: Strate T, Mann O, Kleinhans H, et al. Microcirculatory function and tissue damage is improved after therapeutic injection of bovine hemoglobin in severe acute rodent pancreatitis. Pancreas 2005;30: Klar E, Schratt W, Foitzik T, Buhr H, Herfarth C, Messmer K. Impact of microcirculatory flow pattern changes on the development of acute edematous and necrotizing pancreatitis in rabbit pancreas. Dig Dis Sci 1994;39: Forg cs B, Eibl G, Faulhaber J, Kahrau S, Buhr H, Foitzik T. Effect of fluid resuscitation with and without endothelin A receptor blockade on hemoconcentration and organ function in experimental pancreatitis. Eur Surg Res 2000;32: de-madaria E, Soler-Sala G, S a nchez-paya, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol 2011;106: Mao EQ, Fei J, Peng YB, Huang J, Tang YQ, Zhang SD. Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis. Chin Med J 2010;123: Eckerwall G, Olin H, Andersson B, Andersson R. Fluid resuscitation and nutritional support during severe acute pancreatitis in the past: what have we learned and how can we do better? Clin Nutr 2006;25: Jakobs R, Adamek MU, von Bubnoff AC, Riemann JF. Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study. Scand J Gastroenterol 2000;35: Kahl S, Zimmermann S, Pross M, Schulz HU, Schmidt U, Malfertheiner P. Procaine hydrochloride fails to relieve pain in patients with acute pancreatitis. Digestion 2004;69: Peiro AM, Martı nez J, Martı nez E, et al. Efficacy and tolerance of metamizole versus morphine for acute pancreatitis pain. Pancreatology 2008;8: Morimoto T, Noguchi Y, Sakai T, Shimbo T, Fukui T. Acute pancreatitis and the role of histamine-2 receptor antagonists: a meta-analysis of randomized controlled trials of cimetidine. Eur J Gastroenterol Hepatol 2002;14: ESPEN Guidelines on Parenteral Nutrition: pancreas. Clin Nutr 2009;28: Marik PE, Zaloga GP. Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis. BMJ 2004;328: McClave SA, Greene LM, Snider HL, et al. Comparison of the safety of early enteral vs parenteral nutrition in mild acute pancreatitis. JPEN J Parenter Enteral Nutr 1997;21: Windsor AC, Kanwar S, Li AG, et al. Compared with parenteral nutrition, enteral feeding attenuates the acute phase response and improves disease severity in acute pancreatitis. Gut 1998;42: Kalfarentzos F, Kehagias J, Mead N, Kokkinis K, Gogos CA. Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 1997;84: Ol h A, Pardavi G, Bel gyi T, Nagy A, Issekutz A, Mohamed GE. Early nasojejunal feeding in acute pancreatitis is associated with a lower complication rate. Nutrition 2002;18: Abou-Assi S, Craig K, O Keefe SJ. Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study. Am J Gastroenterol 2002;97: Gupta R, Patel K, Calder PC, Yaqoob P, Primrose JN, Johnson CD. A randomised clinical trial to assess the effect of total enteral and parenteral nutritional support on metabolic, inflammatory and oxidative markers in patients with predicted severe acute pancreatitis (APACHE II C 6). Pancreatology 2003;3: Al-Omran M, Groof A,Wilke D. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev 2003:CD Petrov MS, Correia MI, Windsor JA. Nasogastric tube feeding in predicted severe acute pancreatitis. A systematic review of the literature to determine safety and tolerance. JOP 2008;9: Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. Am J Gastroenterol 2005;100: Golub R, Siddiqi F, Pohl D. Role of antibiotics in acute pancreatitis: a meta-analysis. J Gastrointest Surg 1998;2: Sharma VK, Howden CW. Prophylactic antibiotic administration reduces sepsis and mortality in acute necrotizing pancreatitis: a meta-analysis. Pancreas 2001;22: Villatoro E, Larvin M, Bassi C. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in

30 이태훈외 2 명 30 acute pancreatitis. Cochrane Database Syst Rev 2003;19: CD Villatoro E, Bassi C, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev 2006;4: CD Bai Y, Gao J, Zou D, Li ZS. Prophylactic antibiotics cannot reduce infected pancreatic necrosis and mortality in acute necrotizing pancreatitis: evidence from a meta-analysis of randomized controlled trials. Am J Gastroenterol 2008;103: de Vries AC, Besselink MG, Buskens E, et al. Randomized controlled trials of antibiotic prophylaxis in severe acute pancreatitis: relationship between methodological quality and outcome. Pancreatology 2007;7: Gloor B, Muller CA, Worni M, et al. Pancreatic infection in severe pancreatitis. The role of fungus and multiresistant organisms. Arch Surg 2001;136: Isenmann R, Schwarz M, Rau B, Trautmann M, Schober W, Beger HG. Characteristics of infection with candida species in patients with necrotizing pancreatitis. World J Surg 2002;25: De Waele JJ, Vogelaers D, Blot S, Colardyn F. Fungal infections in patients with severe acute pancreatitis and the use of prophylactic therapy. Clin Infect Dis 2003;37: Conner S, Alexakis N, Neal T, et al. Fungal infection but not type of bacterial infection is associated with a high mortality in primary and secondary infected pancreatic necrosis. Dig Surg 2004;21: Shrikhande S, Friess H, Issengger C, et al. Fluconazole penetration into the pancreas. Antimicrob Agents Chemother 2000;44: He YM, Lv XS, Ai ZL, et al. Prevention and therapy of fungal infection in severe acute pancreatitis: a prospective clinical study. World J Gastroenterol 2003;9: Johnson CD, Kingsnorth AN, Imrie CW, et al. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Gut 2001;48: Uhl W, B chler MW, Malfertheiner P, Beger HG, Adler G, Gaus W. A randomised, double blind, multicentre trial of octreotide in moderate to severe acute pancreatitis. Gut 1999;45: Buchler M, Malfertheiner P, Uhl W, et al. Gabexate mesilate in human acute pancreatitis. German Pancreatitis Study Group. Gastroenterology 1993;104: Seta T, Noguchi Y, Shimada T, Shikata S, Fukui T. Treatment of acute pancreatitis with protease inhibitors: a meta-analysis. Eur J Gastroenterol Hepatol 2004;16: Chen HM, Chen JC, Hwang TL, Jan YY, Chen MF. Prospective and randomized study of gabexate mesilate for the treatment of severe acute pancreatitis with organ dysfunction. Hepatogastroenterology 2000;47: Andriulli A, Leandro G, Clemente R, et al. Meta-analysis of somatostatin, octreotide and gabexate mesilate in the therapy of acute pancreatitis. Aliment Pharmacol Ther 1998;12: Otsuki M, Hirota M, Arata S. Research Committee of Intractable Diseases of the Pancreas. World J Gastroenterol 2006;12:

31 REVIEW ARTICLE pissn eissn THE KOREAN JOURNAL OF PANCREAS AND BILIARY TRACT 급성췌장염진료권고안 : 급성췌장염의국소합병증과괴사성췌장염의치료 김태현 1, 서동완 2, 이승옥 3, 김성훈 3 1 원광대학교의과대학내과, 2 울산대학교의과대학서울아산병원내과, 3 전북대학교의학전문대학원내과 Clinical Practice Guideline for Acute Pancreatitis: The Treatment of Local Complication of Acute Pancreatitis and Necrotizing Pancreatitis Tae Hyeon Kim, M.D. 1, Dong Wan Seo,M.D. 2, Seung-Ok Lee, M.D. 3, Seong Hun Kim,M.D. 3 1 Department of Internal Medicine, Wonkwang University College of Medicine, Iksan, Korea 2 Division of Gastroenterology, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 3 Department of Internal Medicine and Research Institute of Clinical Medicine, Chonbuk National University Hospital and Medical School, Jeonju, Korea Acute pancreatitis is a common and potentially lethal disease. It is associated with significant morbidity and consumes enormous health care resources. Over the last two decades, the treatment of acute pancreatitis has undergone fundamental changes based on new conceptual insights and evidence from clinical studies. The majority of patients with necrotizing pancreatitis have sterile necrosis, which can be successfully treated conservatively. Patients with infected necrosis generally need to undergo an intervention which should ideally be delayed as long as possible, preferably 4 weeks or longer after the onset of disease, for better demarcation and liquefaction of the necrosis. Intervention has shifted from primary open necrosectomy in an early disease stage to a step-up approach, starting with catheter drainage, if needed followed by minimally invasive surgical or endoscopic necrosectomy. Interventional treatment such as percutaneous drainage or endoscopic drainage or surgery should be performed for pancreatic pseudocysts that give rise to symptoms and accompany complications. Applicability of these techniques depends on the availability of specialized expertise and a multidisciplinary team dedicated to the management of severe acute pancreatitis and its complications. This guideline review provides an overview of current standards for conservative and invasive treatment of necrotizing pancreatitis and its local complication such as pseudocyst and abscess. Key words: necrotizing pancreatitis, sterile pancreatic necrosis, infected pancreatic necrosis, pancreatic pseudocyst, pancreatic abscess 1) 서론 Correspongding author. 김태현전북익산시신용동 원광대학병원소화기내과 Tel: [email protected] 급성췌장염의임상적인경과는경증에서중증까지다양하고, 췌장염의조직학적형태에따라서간질성 (interstitial) 췌장염과괴사성 (necrotizing) 췌장염으로분류된다. 급성췌장염의 80-90% 를차지하는간질성췌 31

32 김태현외 4 인 32 장염은대부분보존적치료만으로도호전된다. 그러나급성췌장염의 10-20% 를차지하는괴사성췌장염은사망률이 14-25% 에이르고, 1 괴사성췌장염의 20-35% 에서감염이동반될수있어사망률이더욱증가된다. 특히이들환자에서괴사된췌장부위의 2차적인감염은패혈증과다장기부전으로발전되므로정확한진단과중재적시술이나수술적치료가필요로한다. 또한급성췌장염발생후 4 주가지나면췌장주위합병증들, 즉가성낭종 (pseudocyst), 췌장농양 (pancreatic abscess) 등이발생할수있다. 예후가불량한괴사성췌장염과췌장주위합병증들에대한세심한관리와치료가급성췌장염환자의사망률을감소시키는데매우중요하다. 이질환에대한치료로고전적인개복수술을통한괴사제거술뿐만아니라내시경적배액술, 경피적배액술, 복강경수술등이다양하게제시되고있다. 최근에는괴사성췌장염과합병증에대한치료가개복수술보다는최소침습수술이나시술과내과적치료로이동하고있는경향이다. 급성췌장염은우리나라의대표적인췌장질환이지만진단, 치료에관한국내의료환경에맞는진료가이드라인이없는실정이다. 괴사성췌장염과주위합병증에대한치료근거를제시하기위한국내문헌은매우제한적이어서문헌검색을통하여외국에서제안하는가이드라인과근거문헌들을살펴보았다. 여러외국의가이드라인들은환자의인구학적차이, 선별검사의질과양적차이, 그리고표준화된치료방법의부재등유사연구간에도매우이질적인요소들이존재할수있다. 급성췌장염에관한해외진료지침들의질 (quality) 을 Grill, Shaneyfelt, Agree 도구들을이용하여평가한보고에서최근발표된미국 2, 영국 3, 이탈리아 4 및일본 5,6 의가이드라인이비교적높은점수를받았다. 7 따라서본고에서는이가이드라인들은바탕으로우리나라의적합한급성괴사성췌장염과국소합병증에대한진료가이드라인을제안하였다. 본론 1. 무균성괴사의치료 (Treatment of Sterile Necrosis) 췌장의괴사된부위가지속되면감염의위험성과염증반응이증가할수있다는근거하에과거에는개복수술로괴사된부위를제거하는방법이표준적치료법이었다. 최근 20여년동안의무균성췌장괴사의치료에관한여러 연구들을근거로무균성췌장괴사를가진환자에서는췌장염발생 2-3주내에는내과적치료가표준치료로자리잡고있다. 8 몇몇후향적연구들에서수술적괴사제거술을조기에시행하는것보다연기하거나수술을시행하지않았을때합병증발생률과사망률이적었다고보고하였다 무균성괴사에서수술적치료가시행되었을때감염성괴사가발생하거나추가적인수술이더필요로하게되었다. 3,9,12-14 미국 2, 영국 3, 이탈리아 4 및일본 5,6 의가이드라인에서도이들환자에서내과적보존적치료를권장하고있다. 무균성췌장궤사의의인성감염은중재적시술이추가되고이환율과사망률이증가될수있어최대한보존적인치료가필요하다. 그러나췌장주위수액고임 (peripancreatic fluid collection) 때문에지속적인위장관폐쇄로임상적인증상, 즉반복적인오심과구토등이발생하면중재적시술이필요할수있다. 이경우에도중재적시술은임상적인증상과복부 CT를참고하며가능한증상발생후 4-6주까지연기해야한다. 그이후복통이지속되거나다장기부전이발생하면괴사제거술이고려될수있다. 무균성괴사를가진환자들에서적어도 2-3주지나면후복막에전반적인염증이호전되어괴사된췌장과췌장주위에잘싸여진구조물이형성된다. 15 이구조물이형성되는시기에도달하면장기부전도호전되고대부분환자들의증상도소실되어추가적인치료가필요로하지않는다. 그러나집중보존적치료에반응이없는경우에는수술적치료나중재적시술이필요할수있다. 2-3주후에는막으로잘싸여진낭성구조물이형성되어있어구조물내의수액흡인과위의후벽과구조물의문합술이용이하게된다. 2 또한이구조물과위벽이잘밀착되어있어내시경초음파유도하경벽적배액술도시행될수있다. 16 이배액통로를더욱확장하여내시경을삽입한후괴사된조직들을제거할수있고강내에내시경적비강배액관을삽입하여지속적으로생리식염수로세척을할수있다. 괴사제거는내시경적시술뿐만아니라병원의시설과전문인력에따라서수술적방법이나경피적방법도시행될수있다. 괴사제거술후췌관루또는췌즙누출이발생하면수술적또는내시경적치료가필요할수있다. 첫 2-3주내조기에수술적치료가필요한경우는드물지만다음과같다. 8,17 첫째로복압이매우증가하여복부팽만이심해지는 abdominal compartment syndrome으

33 급성췌장염진료권고안 : 급성췌장염의국소합병증과괴사성췌장염의치료 33 로즉각적인개복수술이필요하다. 둘째는췌장주위염증의확대로인하여주위의소장이나대장의천공이다. 셋째는가성동맥류로부터출혈이혈관중재술로지혈이실패한경우이다. 권고사항 1. 무균성췌장괴사는첫 2-3주동안에는보존적 ( 내과적 ) 치료가최우선이다. -권고등급: B -동의수준: 전적으로동의함 (51%), 대체로동의함 (49%), 일부동의함 (0%), 전적으로동의하지않음 (0%). 2. 무균성췌장괴사환자에서보존적치료에도불구하고그이후복통이지속되거나다장기부전이발생하면괴사제거술이필요하다. -권고등급: B -동의수준: 전적으로동의함 (26%), 대체로동의함 (58%), 일부동의함 (15%), 전적으로동의하지않음 (1%). 2. 감염성췌장궤사 (Infected pancreatic necrosis) 1) 진단괴사성췌장염에서 2차적감염은어느시기에도발생할수있지만보통증상발현약 2-4주후에주로발생한다. 복부영상에서췌장괴사부위에공기음영이관찰되면강력하게감염을의심할수있고, 괴사조직이나주위수액의균동정으로감염을증명할수있다. 균감염은복부전산화단층촬영 (computerized tomography, CT) 또는초음파유도하세침흡인 (fine needle aspiration, FNA) 을통하여진단될수있고, 이시술의진단정확도는 % 로높다. 18,19 이시술의위음성률이 20-25% 라는보고도있어, 20 이시술을시행해야할적절한시기, 회수, 적응증에대하여논란이많은상태이다. 21 과거에는감염성췌장궤사의치료로즉각적인수술적괴사제거술이필요하여 FNA을통한균동정이필수적이었다. 그러나최근에는패혈증이없으면항생제와보존적치료만으로도감염성췌장염의치료도가능하고, 최소침습중재시술, 즉내시경적또는경피적배액술등이수술보다우선적으로시행되고있다. 따라서중재적시술을시행할때, 세균과곰팡이균주의배양이이루어질수있어단순한진단만을위한 FNA 의필요성이점차감소되고있다. 하지만미국, 일본, 영국가이드라인은모두정확한진단을위하여 CT나복부초음파유도하 FNA가필요하다고하였다. 특히영국가이드라인에서구체적으로췌장염발생 7-14일후 30% 이상의췌장괴사가존재하고패혈증의임상적소견이있으면영상유도하세균배양을위한 FNA 가필요하다고하였다. 최근치료의방향이변화하고있어 FNA의필요성이감소하고있지만아직이부분에대한근거가부족한상태여서기존의권고사항을유지하였다. 권고사항패혈증을동반한괴사성췌장염환자에서감염성췌장궤사를진단하기위해서는 CT 또는초음파유도하세침흡인으로얻은검체에서 Gram's stain과배양이필요하다. -권고등급: B -동의수준: 전적으로동의함 (26%), 대체로동의함 (56%), 일부동의함 (15%), 전적으로동의하지않음 (3%). 2) 수술적괴사제거술과수술시기감염성췌장괴사의치료는괴사된췌장이나췌장주위조직을제거하는것이기본적인치료법이고, 과거에는주로개복을통한조기수술이시행되었다. 수술적괴사제거술이그동안권장된이유는감염된괴사조직을제거할수있고, 괴사된조직내로잘침투되는항생제가없었고, 대부분의환자들이조기에처치가필요한불안정한상태였기때문이다. 여러가지수술방법에따라서수술후경과가다르지만이환율 40-89%, 사망률 10-47% 로높았다 수술의높은사망률과이환율을극복하기위해서여러가지중재적치료, 즉내시경적치료또는경피적치료가대두되고있다. 조기수술에대한효과에대한의문이제기되면서지연수술과조기수술을비교하는보고들이있어왔다. 한후향적연구에서급성괴사성췌장염환자중지연수술군에비하여조기수술군에서사망률 (12% vs. 39%) 이통계학적으로의미있게높았다. 11 조기수술과지연수술군을무작위비교한연구에따르면조기수술군사망률이 56%, 지연수술군사망률은 27% 로의미있는차이를보여주지는못했지만조기수술을받은환자에서사망률이너무높아연구가중단되었다. 26 급성췌장염으로수술적치료를받은

34 김태현외 4 인 34 환자들의예후에영향을주는요소들을후향적연구에서는 56명의환자중 22명이조기수술 ( 췌장염발생 12일내 ) 을받았고, 34명이지연수술 ( 췌장염발생 12일이후 ) 을받았는데, 조기수술군과지연수술군의사망률이각각 54.5%, 29.4% 였다 (p=0.06). 27 괴사성췌장염으로수술을받은 53 명을대상으로한수술시기에관한연구에서발병 14일안에수술을받은군의사망률은 75%, 일사이에수술을받은수술군의사망률은 45%, 30일이후수술군의사망률은 8% 였다 (p=0.001) 년발표된 International Association of Pancreatology (IAP) 의진료지침에따른지연수술과그전에시행한조기수술성적을비교한연구에서는 IAP 진료지침에따른지연수술의이환율과사망률이각각 72%, 4% 로의미있게낮았다. 25 괴사성췌장염의치료성적에관한 11개의논문에포함된 1,136 명을대상으로한메타분석에서발병후지연수술보다는조기에수술하면할수록사망률이높았다. 29 이연구결과들은가능한수술을지연하는것이환자의사망률을감소시킬수있음을강조하고있다. 3) 보존적치료괴사성췌장염환자에서중재적시술또는수술적치료는췌장염발생 3-4주후로최대한연기해야사망률과합병증을줄일수있다. 30,31 감염성췌장괴사환자에서중재적시술을연기하기위해서는처음에는항생제치료와최대한보존적치료가이루어져야한다. 감염성췌장괴사에대한일차적보존적치료의우수한결과를보고하는증례보고들이있어왔다. Runzi 등 32 의보고에서는괴사성췌장염 88례중감염성괴사로 28명이진단되었다. 이들중항생제와보존적치료를평균 5주를받은후수술적괴사제거술을받았던 12명중 2명 (16%) 과단지항생제와보존적치료를받은나머지 16명중 2명 (12%) 에서사망이발생하였다. 다른보고에서는감염성췌장괴사환자 24명중전신상태가불안정한 18명에서괴사제거술이시행되어사망이 5명 (28%) 에서발생하였고, 비교적안정된환자 6명은수술적치료없이모두회복되었다. 33 국내보고에서는감염성췌장염 31명중 23명에서경피적 (18명) 또는내시경적 (5명) 배액술을시행받았고, 이들중 5명이전신상태악화로괴사제거술을받았지만 1명사망하였으며, 초기치료로항생제를투여받았던 8명에서는더이상의추가치료가필요없었다. 34 최근에보고된감염성췌장염치료에관한 8개의논문을대상으로한메타분석에서일차적 으로보존적치료를받았던환자군의치료성공률은 64%, 사망률은 12%, 괴사제거술이필요한경우는 26% 였다. 35 결국상기보고들을보면감염성췌장괴사환자에서전신상태가안정적이면보존적치료가일차적치료가될수있음을시사하고있다. 췌장염발생 4주가지나면괴사조직이살아있는조직으로부터경계구분 (demarcation) 이잘되어져수술중출혈등과같은합병증을줄일수있고, 살아있는조직의절제를최소화하여수술후내분비기능과외분비기능의장애를예방할수있을뿐만아니라수술후여러가지부작용을감소시킬수있다. 12 4) 최소침습치료 (Minimal invasive treatment) 와수술적치료괴사성췌장염환자에서수술적또는중재적시술의적응증은감염성췌장궤사라고현재까지널리알려지고있고각나라별진료지침에서도인정되고있다. 2,3,10,30,31 최근에는개복수술에따르는높은사망률과합병증을줄이고, 대부분패혈증과다발성장기부전에의한중증췌장염환자들에게수술스트레스를최소화하기위해서다양한경로를통한최소침습 (minimal invasive) 시술들이시행되고있고기존의개복수술보다더좋은결과들을보고하고있다. 8,36-40 지금까지보고된괴사성췌장염에대한최소침습술식은경피적배액법, 내시경적배액법, 복강경을이용한괴사제거술등이있다. 경피적중재방사선적치료는 French 대구경의경피도관을좌측복벽을통하여후복강내의병변부위에삽입하여적극적인세척과배액하는방법이다. 41 후복막접근방식은일반적으로오염과장관유출을피할수있고, 후에 step-up 접근을위한초석이될수있어많이이용되고있다. 체계적인문헌검토로보고한경피적배액술을받은 381명의괴사성췌장염환자에서 17.4% 의사망률을보고하였고, 변연절제술 (debridement) 없이도경피적배액만으로치료할수있다고보고하였다. 42 필요에따라서는이통로를통하여내시경을삽입하여괴사된물질을제거할수있고, 수술의가교 (bridge) 역할로이용될수있다. 43 최근에는감염성췌장괴사환자들에서최소침습후복막괴사제거술 (minimal invasive retroperitoneal necrosectomy) 이보고되고있다. 가장많이사용되는술기들은동관 (sinus tract) 을통한경피적괴사제거술, 복강경경복부괴사제거술 (laparoscopic trans-abdominal necrosectomy), 비디오매개후복막변연절제술

35 급성췌장염진료권고안 : 급성췌장염의국소합병증과괴사성췌장염의치료 35 (video-assisted retroperitoneal debridement, VARD) 등이있다. Sinus tract endoscopy 를이용한괴사제거술의이환율은 25-88%, 사망률은 0-25% 로다양하게보고되고있고, 41,44 VARD는 sinus tract endoscopy와 open lumbar approach 의융합방식으로이환율이 24-54%, 사망률이 0-8% 로보고되고있다. 45,46 VARD 장점은일반적인수술장비를사용하는반개복 (semi-open) 시술이고, 대부분한번으로종료될수있다는점이다. 내시경초음파시술의발전과더불어내시경적배액술이보편화되면서내시경적괴사제거술도많이사용되고있다. 내시경적시술은전신마취없이수면유도상태에서가능하고염증을감소시킬수있고새로운다장기부전과같은합병증을막을수있다. 일반적으로내시경초음파유도하에위나십이지장벽을통하여병변부위를천자한후경벽적통로를확장하여내시경을삽입한다음괴사제거술을시행한다. 이방법에관한 10개의문헌들을체계적으로분석한보고에서사망률은 5%, 이환율은 27% 였고, 평균시술횟수는 4회였다. 47 이보고는매우좋은성적을보고하고있지만감염성괴사환자에서중증의환자가많지않다는치우침 (bias) 을내포하고있다. 최근수술적치료와내시경적치료를비교한무작위연구에서는주요합병증과사망률이수술적치료에비해서의미있게적었다고보고하였다. 48 급성췌장발생 4주가지나면감염된괴사조직과끈끈한고름이막으로잘싸여지고막이두꺼워져 (wall-off necrosis) 내시경적괴사제거술이합병증없이효과적으로시행될수있다. 49,50 이경우에내시경적치료의성공률은 73-92% 로보고되고있다. 51,52 경피적배액법이나내시경적배액법은성공적인배액을위해서는많은횟수의시술과시간이필요하고, 가는배액관으로고형의괴사조직파편 (debris) 들이배액되는데제한점이있어광범위한괴사를치료하는데는한계점이있다. 그러나복강경을이용한괴사제거술은작은상처를통하여광범위하게괴사부위를제거할수있는장점이있다. Connor 등 53 은개복수술을받은 41명과복강경수술을받은 47명의경과를분석한후향적연구에서수술시행횟수, 수술후중환자실체류기간, 재원기간, 사망률에서통계적으로유의하게복강경수술이우수하였다고보고하였다. 감염성췌장괴사환자에서경피적배액이나내시경적배액술로감염된괴사부위를배액하고도임상적인증상과증후의호전이없으면, 다음단계로복강경이나내시경을 이용한최소침습괴사제거술을추가적으로시행하는단계적 (Step-up) 접근방식이이용될수있다. 54 첫단계의배액관을이용한배액은패혈증을경감하고괴사제거술을연기하거나피할수있다. 88명의감염성췌장괴사환자들에서기존의개복수술과수술적 step-up 치료 ( 경피적배액술, 최소침습후복막괴사제거술 ) 를비교한연구에서주요합병증발생율 ( 다장기부전, 장피부누공, 장천공 ) 이 step-up 방식군이 40%, 수술적치료군이 69% 로의미있는차이가있었지만, 사망률에는양군간에 (19% vs. 16%) 의미있는차이가없었다. 54 또한경피적배액만으로도 35% 환자에서더이상의수술적치료없이호전되었다. 이와같은비침습적인치료는수술적괴사제거술을연기하거나피할수있는장점이있다. 11,55 결론적으로감염성췌장괴사에환자에서초기에는항생제투여와보존적치료를하여괴사제거술을가능하면최대한지연하고임상적상황이악화되거나패혈증으로진행하는소견이보이면괴사부위의배액술과괴사제거술이시행될수있다. 급성췌장염발병후 4-6 주가지나면정상췌장과괴사된췌장의경계구분이분명해지고괴사부분이액화되므로괴사제거술이용이하고괴사제거술의합병증을최소화할수있다. 괴사제거술이나배액방법은병원시술과병원의전문가유무에따라결정될수있다. 권고사항 1. 감염성췌장괴사는수술적치료, 경피적중재술, 내시경적중재술의적응증이다. -권고등급: B -동의수준: 전적으로동의함 (50%), 대체로동의함 (45%), 일부동의함 (6%), 전적으로동의하지않음 (0%) 2. 환자의상태가안정된감염성췌장괴사의경우에는항생제치료와보존적치료를하면서추적관찰할수있다. -권고등급: B -동의수준: 전적으로동의함 (27%), 대체로동의함 (64%), 일부동의함 (9%), 전적으로동의하지않음 (1%). 3. 감염성췌장괴사환자에서보존적치료에도불구하고임상적상황의악화나패혈증의증후가보이면중재적배액술이나괴사제거술이시행되어야한다. -권고등급: C

36 김태현외 4 인 36 -동의수준: 전적으로동의함 (49%), 대체로동의함 (47%), 일부동의함 (5%), 전적으로동의하지않음 (0%). 4. 괴사성췌장염에서수술적치료는췌장염발생 4주후로최대한연기하여야한다. -권고등급: B -동의수준: 전적으로동의함 (29%), 대체로동의함 (62%), 일부동의함 (8%), 전적으로동의하지않음 (2%). 5. 수술적괴사제거술전경피적또는내시경적배액술을시행하여가능한수술적괴사제거술을피하거나연기할수있다. -권고등급: B -동의수준: 전적으로동의함 (32%), 대체로동의함 (66%), 일부동의함 (2%), 전적으로동의하지않음 (0%). 4) 괴사제거술후장기추적 (Long-term follow-up of after necrosectomy) 괴사성췌장염으로괴사제거술을받은 63명의환자에서수술후장기간추적 ( 평균추적기간 : 28.9 개월 ) 연구에서췌장기능이상을제외한합병증이 39명 (62%) 에서발생하였다. 56 합병증으로는췌장루 8예, 담도협착 4예, 가성낭종 5예, 췌장의외분비기능장애 25%, 당뇨 33% 에서발생하였다. 췌장괴사제거술을받은 98명을대상으로한다른연구에서는주췌관의협착으로 14.3% 에서재발성췌장염이발생하여수술적치료가필요하였다. 중증의담석성괴사성췌장염으로치료받은 39명을괴사제거술을받은군 (12명) 과그렇지않는군 (15명) 으로구분하여전향적코호트연구를시행하였다. 57 이보고에서지방변과인슐린대체치료가괴사제거술군에서만각각 25% 와 33.3% 에서발생하였다. 상기연구들을토대로보면괴사제거술을받은환자들은췌관협착, 담도협착, 그리고외분비및내분비췌장기능에대한장기간추적이필요함을알수있다. 권고등급췌장괴사제거술후에는담도협착, 췌관협착, 췌장의내분비와외분비기능장애에대한장기간동안추적검사가필요하다. -권고등급: B -동의수준: 전적으로동의함 (35%), 대체로동의함 (58%), 일부동의함 (7%), 전적으로동의하지않음 (0%). 3. 췌장가성낭종 (Pancreatic pseudocysts) 1) 췌장가성낭종배액술의적응증 (Indication for drainage treatment in pancreatic pseudocysts) 급성췌장염후발생하는가성낭종은보통최소 4주이후형성된다. 발생기전은급성췌장염발생후췌관에서췌장액이누출되어췌장실질이나췌장주위지방이괴사된부위가액화되면서발생할수있다. 58 과거에는가성낭종의크기가 6주이상지속되거나가성낭종의크기가 6 cm 이상이면자발적소실확률이적으므로배액의적응증으로인식되어왔다. 59,60 최근장기간가성낭종의추적관찰한연구에서 86% 에서자발적소실이있었고합병증발생율은 3-9% 이므로장기간관찰이안전하고효과적이었다. 61 또한낭종의크기가가성낭종의합병증발생에중대한영향을주지않는다고보고하였다. 61,62 따라서내시경적배액술이필요한적응증은가성낭종으로인해복통이발생하는경우, 가성낭종의크기가점점커질때, 감염성가성낭종, 가성낭종내출혈, 가성낭종에의한장이나총담관의폐쇄가있는경우이다. 배액술을결정하기전고려해야할점은낭종성종양과감별이므로췌장염의병력이명확하지않거나영상소견에서가성낭종의가능성이낮다면 EUS-FNA 을통한낭종의수액분석이필요할수있다. 2) 췌장가성낭종의중재적치료 (Interventional treatment selected forpancreatic pseudocysts) 췌장가성낭종의치료방법은경피적배액술, 내시경적배액술, 수술적배액술이있다. 경피적배액술의치료성공률은 % 로높아수술적치료를대체할수있다. 이시술은간단하고비침습적인시술이지만재발율은 7%, 합병증발생율은 18%, 피부-췌루형성빈도가 11-39% 로다양하다 가성낭종의완치율은수술적치료가경피적치료에비하여높다는보고도있다. 66,67 가성낭종에대한경피적치료와수술적치료를비교한한전향적연구에서일단계치유율은각각 77% (20/26), 73%(18/26) 였고, 치료방법에따른재발률과완치율은차이가없었다. 68 배액의효과가있었던경피적배액관의평균유치기간은 일이었다. 69,70 따라서이기간이지나도가성낭종이

37 급성췌장염진료권고안 : 급성췌장염의국소합병증과괴사성췌장염의치료 37 지속되면수술적치료가고려되어야한다. 경피적치료와내시경적치료로가성낭종을효과적으로배액하기위해서는췌관이정상이거나췌관협착이존재하지만낭종과췌관의교통이없어야한다. 71 반면에내시경적경유두적배액술은췌관과낭종이연결이되어있을때이용될수있다. 가성낭종에대한내시경배액방법은위벽을통한방법 (endoscopic cystogastrostomy), 십이지장벽을통한방법 (endoscopic cystoduodenostomy), 그리고유두를통한방법 (transpapillary drainage) 이있다. 내시경배액방법의성공률은 %, 합병증발생률은 4-33%, 재발률은 4-30% 로보고되었다. 16,72-74 이시술은경피적치료에비하여피부-췌누공을피할수있다는장점이있지만, 내시경치료의성적이시술자의숙련도에따라다를수있다는단점이있다. 75 후향적연구이기는하지만수술적치료내시경치료를비교한한보고에서는내시경배액방법의성공률과합병증발생률은수술방법과비슷하였다. 76 최근에는내시경초음파가치료내시경에이용되면서가성낭종의내시경치료가증가하고있다. 위나십이지장에서가장융기된 (bulging) 부위를내시경초음파없이맹목천자 (blind puncture) 하여배액하는방법에비하여내시경초음파로천자부위의주위구조물과목표부위를실시간으로관찰하면서천자를하면목표물과위장사이에존재하는혈관과장기를확인할수있다. 16,77 수술적치료의적응증은보존적치료, 내시경적배액술, 경피적배액술에효과적이지못하거나낭종의감염또는출혈이동반되는경우이다. 수술적치료는낭종과장관사이에누공을만드는방법 (cystogastrostomy, cystojejunostomy) 과낭종절제술으로구분된다. 복강경수술이최근에보고되고있지만 78 더많은연구가필요하다. 가성낭종의배액은경피적이나내시경적시술이우선적으로시행될수있고, 이중재적시술에반응이없으면수술적치료가시행되는추세이다. 그러나 3가지방법의장단점이있으므로치료방법선택은가성낭종의특성과시술자숙련도및시술병원의시설에따라결정해야한다. 권고사항 1. 가성낭종의치료적응증은임상적증상을유발하는낭종, 크기가커지는낭종, 합병증이발생한낭종이다. -권고등급: B -동의수준: 전적으로동의함 (65%), 대체로동의함 (33%), 일부동의함 (2%), 전적으로동의하지않음 (0%). 2. 췌장가성낭종의치료는내시경적배액술, 경피적배액술, 수술적배액술이이용될수있다. 각치료법의선택은낭종의위치, 낭종과췌관의연결유무, 낭종과위장관과해부학적위치관계, 병원의시설에따라서결정될수있다. -권고등급: A -동의수준: 전적으로동의함 (71%), 대체로동의함 (29%), 일부동의함 (0%), 전적으로동의하지않음 (0%). 3. 가성낭종의수술적치료의적응증은출혈성가성낭종과경피적또는내시경적배액술에호전이없는경우이다. -권고등급: C -동의수준: 전적으로동의함 (29%), 대체로동의함 (59%), 일부동의함 (12%), 전적으로동의하지않음 (0%). 4. 췌장농양 (pancreatic abscess) 췌장농양도가성낭종과비슷한특징을가지고있어가성낭종의치료법과큰차이가없어각치료법들의장단점은비슷하다. 또한췌장농양의발생빈도수가많지않아가성낭종에포함되어보고된경우가많고순수하게췌장농양만보고한문헌은많지않다. 췌장농양의대부분은액화된상태가대부분이고, 경피적배액술은 78-86% 의치료성적을보고하고있다. 79,80 Venu 등 81의보고에의하면내시경배액술의치료성공률은조기에는 94% 였고추적기간후에는 74% 였다. 35 명을대상으로한다른보고에서는치료성공률은 80% 였고 7명에서수술적치료가추가되었다. 82 대부분의보고들이소수의환자들을대상으로한연구들이어서많은증례를축적한장기간추적연구가필요하다. 췌장농양에대한경피적또는내시경적치료에서좋은결과를발표한보고들은후향적증례연구들이다. 이들방법의치료성적이 80% 내외의좋은치료성적을보고하고있지만 Ransonscore 가 5점이상인중증이나다발성농양의경우에경피적치료의조기치료율은 30-47% 로낮다. 68,83 농양의경피적또는내시경적배액에도불구하고감염의임상적증후가지속되면수술적배액술이필요하다. 또

38 김태현외 4 인 38 한경피적배액술에더하여경피경위배액술이나내시경적배액술이추가적으로시도될수있다. 그러나이들치료방법들의효과를입증하기위해서는더많은증례를통한연구가필요하다. 권고사항췌장농양에서는내시경적배액술, 경피적배액술, 수술적치료가시행될수있다. 각치료법의선택은농양의위치, 농양과위장관과해부학적위치관계, 병원의시설에따라서결정될수있다. -권고등급: B -동의수준: 전적으로동의함 (52%), 대체로동의함 (48%), 일부동의함 (0%), 전적으로동의하지않음 (0%). 결론 괴사성췌장염의치료부분이최근에큰진전이있어왔지만아직도해결해야될난제들이많이존재한다. 괴사성췌장염의약 2/3에서는보존적치료만으로도성공적으로호전될수있다. 무균성췌장궤사에서는불필요한중재적시술을피하는것이감염이나감염과연관된여러가지합병증들을최소화할수있다. 감염성췌장괴사에서는감염된괴사된부분이액화되고잘경계가만들어지는급성췌장염발생 4주후까지최대한보존적치료를시행하여괴사제거술을연기하는것이환자의예후에좋을것으로알려지고있다. 수술적괴사제거술을피하거나연기하기위해서경피적또는내시경적배액술이우선적으로시행될수있다. 이시술로도호전이없으면위나십이지장의경벽적통로나경피적통로를통한내시경을이용한괴사제거술또는개복수술을시행하는단계적접근법 (step-up) 이시행될수있다. 임상적증상이있는췌장가성낭종이나농양은경피적또는내시경적배액이필요하고이러한중재술에도불구하고감염의임상적증후가지속되면수술적배액술이필요하다. 이러한중재적시술과수술을위해서는소화기내과, 외과, 중재적방사선전문가들과의긴밀한협조가필요하다. 국문초록 급성췌장염은대부분경증으로호전되지만중증의경우에는높은이환율과의료비용의상승을초래할수있다. 지난 20년간급성췌장염에대한새로운개념정립을근간으로치료에있어서도많은변화가있어왔다. 괴사성췌장염의대부분은무균성으로보존적치료로호전되지만괴사성췌장염에감염이동반되면중재적시술이나수술적치료가필요할수있다. 그러나감염된괴사된부분이액화되고경계막이잘만들어지는췌장염발생 4주후까지최대한보존적치료를하면서중재적시술이나수술적치료를연기해야한다. 수술적치료를조기에시행하기보다는감염된부위를배액하는경피적또는내시경중재술을시행하여염증과감염을최소화하고, 필요하면다음단계로복강경이나내시경을이용한최소침습괴사제거술또는수술적괴사제거술을추가적으로시행하는단계적접근법이이용될수있다. 임상적증상이나합병증을동반한가성낭종이나췌장농양은경피적, 내시경적, 수술적배액술이필요하다. 이다양한치료법들중적절한방법의선택은병변의특성과시술자숙련도및시술병원의시설에따라결정할수있다. 이문헌에서는급성괴사성췌장염과국소합병증에관한보존적치료와침습적치료에관한최근경향을기술하였다. 색인단어 : 괴사성췌장염, 무균성췌장괴사, 감염성췌장괴사, 췌장가성낭종, 췌장농양 참고문헌 1. Sekimoto M, Shikata S, Takada T, et al. Changes in management of acute pancreatitis before and after the publication of evidence-based practice guidelines in J Hepatobiliary Pancreat Sci 2010;17: Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101: UK guidelines for the management of acute pancreatitis. Gut 2005;54(Suppl 3):iii1-iii9. 4. Pezzilli R, Zerbi A, Di Carlo V, Bassi C, Delle Fave GF. Practical guidelines for acute pancreatitis. Pancreatology 2010;10: Takeda K, Yokoe M, Takada T, et al. Assessment of severity of acute pancreatitis according to new prognosticfactors and CT grading. J Hepatobiliary Pancreat Sci 2010;17: Hirota M, Takada T, Kawarada Y, et al. JPN Guidelines

39 급성췌장염진료권고안 : 급성췌장염의국소합병증과괴사성췌장염의치료 39 for the management of acute pancreatitis: severity assessment of acute pancreatitis. J Hepatobiliary Pancreat Surg 2006;13: Loveday BP, Srinivasa S, Vather R, et al. High quantity and variable quality of guidelines for acute pancreatitis: a systematic review. Am J Gastroenterol;105: Werner J, Feuerbach S, Uhl W, Buchler MW. Management of acute pancreatitis: from surgery to interventional intensive care. Gut 2005;54: Connor S, Ghaneh P, Raraty M, et al. Increasing age and APACHE II scores are the main determinants of outcome from pancreatic necrosectomy. Br J Surg 2003;90: Hungness ES, Robb BW, Seeskin C, Hasselgren PO, Luchette FA. Early debridement for necrotizing pancreatitis: is it worthwhile? J Am Coll Surg 2002;194: ; discussion Hartwig W, Maksan SM, Foitzik T, Schmidt J, Herfarth C, Klar E. Reduction in mortality with delayed surgical therapy of severe pancreatitis. J Gastrointest Surg 2002;6: Uhl W, Warshaw A, Imrie C, et al. IAP Guidelines for the Surgical Management of Acute Pancreatitis. Pancreatology 2002;2: Gotzinger P, Wamser P, Barlan M, Sautner T, Jakesz R, Fugger R. Candida infection of local necrosis in severe acute pancreatitis is associated with increased mortality. Shock 2000;14: ; discussion Gotzinger P, Wamser P, Exner R, et al. Surgical treatment of severe acute pancreatitis: timing of operation is crucial for survival. Surg Infect (Larchmt) 2003;4: Baron TH, Harewood GC, Morgan DE, Yates MR. Outcome differences after endoscopic drainage of pancreatic necrosis, acute pancreatic pseudocysts, and chronic pancreatic pseudocysts. Gastrointest Endosc 2002;56: Sriram PV, Kaffes AJ, Rao GV, Reddy DN. Endoscopic ultrasound-guided drainage of pancreatic pseudocysts complicated by portal hypertension or by intervening vessels. Endoscopy 2005;37: Nathens AB, Curtis JR, Beale RJ, et al. Management of the critically ill patient with severe acute pancreatitis. Crit Care Med 2004;32: Banks PA, Gerzof SG, Langevin RE, Silverman SG, Sica GT, Hughes MD. CT-guided aspiration of suspected pancreatic infection: bacteriology and clinical outcome. Int J Pancreatol 1995;18: Rau B, Pralle U, Mayer JM, Beger HG. Role of ultrasonographically guided fine-needle aspiration cytology in the diagnosis of infected pancreatic necrosis. Br J Surg 1998;85: Rodriguez JR, Razo AO, Targarona J, et al. Debridement and closed packing for sterile or infected necrotizing pancreatitis: insights into indications and outcomes in 167 patients. Ann Surg 2008;247: Buchler MW, Gloor B, Muller CA, Friess H, Seiler CA, Uhl W. Acute necrotizing pancreatitis: treatment strategy according to the status of infection. Ann Surg 2000;232: Fernandez-del Castillo C, Rattner DW, Makary MA, Mostafavi A, McGrath D, Warshaw AL. Debridement and closed packing forthe treatment of necrotizing pancreatitis. Ann Surg 1998;228: Olakowski M, Dranka-Bojarowska D, Szlachta- Swiatkowska E, Lekstan A, Lampe P. Management of necrotizing pancreatitis: flexible approach depending on intra-operative assessment of necrosis. Acta Chir Belg 2006;106: Nieuwenhuijs VB, Besselink MG, van Minnen LP, Gooszen HG. Surgical management of acute necrotizing pancreatitis: a 13-year experience and a systematic review. Scand J Gastroenterol Suppl 2003: Howard TJ, Patel JB, Zyromski N, et al. Declining morbidity and mortality rates in the surgical management of pancreatic necrosis. J Gastrointest Surg 2007;11: Mier J, Leon EL, Castillo A, Robledo F, Blanco R. Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg 1997;173: De Waele JJ, Hoste E, Blot SI, et al. Perioperative factors determine outcome after surgery for severe acute pancreatitis. Crit Care 2004;8:R van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 2011;141: Bollen TL, van Santvoort HC, Besselink MG, van Ramshorst B, van Es HW, Gooszen HG. Intense adrenal enhancement in patients with acute pancreatitis and early organ failure. Emerg Radiol 2007;14: Amano H, Takada T, Isaji S, et al. Therapeutic intervention and surgery of acute pancreatitis. J Hepatobiliary Pancreat Sci;17: Pezzilli R, Zerbi A, Di Carlo V, Bassi C, Delle Fave GF. Practical guidelines for acute pancreatitis. Pancreatology 2010;10: Runzi M, Niebel W, Goebell H, Gerken G, Layer P. Severe acute pancreatitis: nonsurgical treatment of infected

40 김태현외 4 인 40 necroses. Pancreas 2005;30: Sivasankar A, Kannan DG, Ravichandran P, Jeswanth S, Balachandar TG, Surendran R. Outcome of severe acute pancreatitis: is there a role for conservative management of infected pancreatic necrosis? Hepatobiliary Pancreat Dis Int 2006;5: Lee JK, Kwak KK, Park JK, et al. The efficacy of nonsurgical treatment of infected pancreatic necrosis. Pancreas 2007;34: Mouli VP, Sreenivas V, Garg PK. Efficacy of Conservative Treatment, Without Necrosectomy, for Infected Pancreatic Necrosis: A Systematic Review and Metaanalysis. Gastroenterology 2012;144: Morise Z, Yamafuji K, Asami A, et al. Direct retroperitoneal open drainage via a long posterior oblique incision for infected necrotizing pancreatitis: report of three cases. Surg Today 2003;33: Carter R. Management of infected necrosis secondary to acute pancreatitis: a balanced role for minimal access techniques. Pancreatology 2003;3: Pamoukian VN, Gagner M. Laparoscopic necrosectomy for acute necrotizing pancreatitis. J Hepatobiliary Pancreat Surg 2001;8: Seewald S, Groth S, Omar S, et al. Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a new safe and effective treatment algorithm (videos). Gastrointest Endosc 2005;62: Bucher P, Pugin F, Morel P. Minimally invasive necrosectomy for infected necrotizing pancreatitis. Pancreas 2008;36: Carter CR, McKay CJ, Imrie CW. Percutaneous necrosectomy and sinus tract endoscopy in the management of infected pancreatic necrosis: an initial experience. Ann Surg 2000;232: van Baal MC, van Santvoort HC, Bollen TL, Bakker OJ, Besselink MG, Gooszen HG. Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis. Br J Surg 2011;98: van Brunschot S, Bakker OJ, Besselink MG, et al. Treatment of necrotizing pancreatitis. Clin Gastroenterol Hepatol 2012;10: Connor S, Ghaneh P, Raraty M, et al. Minimally invasive retroperitoneal pancreatic necrosectomy. Dig Surg 2003;20: van Santvoort HC, Besselink MG, Bollen TL, Buskens E, van Ramshorst B, Gooszen HG. Case-matched comparison of the retroperitoneal approach with laparotomy for necrotizing pancreatitis. World J Surg 2007;31: Horvath K, Freeny P, Escallon J, et al. Safety and efficacy of video-assisted retroperitoneal debridement for infected pancreatic collections: a multicenter, prospective, single-arm phase 2 study. Arch Surg 2010;145: Haghshenasskashani A, Laurence JM, Kwan V, et al. Endoscopic necrosectomy of pancreatic necrosis: a systematic review. Surg Endosc 2011;25: Bakker OJ, van Santvoort HC, van Brunschot S, et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA 2012;307: Coelho D, Ardengh JC, Eulalio JM, Manso JE, Monkemuller K, Coelho JF. Management of infected and sterile pancreatic necrosis by programmed endoscopic necrosectomy. Dig Dis 2008;26: Seewald S, Ang TL, Teng KC, Soehendra N. EUS-guided drainage of pancreatic pseudocysts, abscesses and infected necrosis. Dig Endosc 2009;21(Suppl 1):S61-S Seewald S, Ang TL, Teng KY, et al. Endoscopic ultrasound-guided drainage of abdominal abscesses and infected necrosis. Endoscopy 2009;41: Seifert H, Biermer M, Schmitt W, et al. Transluminal endoscopic necrosectomy after acute pancreatitis: a multicentre study with long-term follow-up (the GEPARD Study). Gut 2009;58: Connor S, Raraty MG, Howes N, et al. Surgery in the treatment of acute pancreatitis-minimal access pancreatic necrosectomy. Scand J Surg 2005;94: van Santvoort HC, Besselink MG, Bakker OJ, et al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med 2010;362: Bhansali SK, Shah SC, Desai SB, Sunawala JD. Infected necrosis complicating acute pancreatitis: experience with 131 cases. Indian J Gastroenterol 2003;22: Connor S, Alexakis N, Raraty MG, et al. Early and late complications after pancreatic necrosectomy. Surgery 2005;137: Sabater L, Pareja E, Aparisi L, et al. Pancreatic function after severe acute biliary pancreatitis: the role of necrosectomy. Pancreas 2004;28: Segal D, Mortele KJ, Banks PA, Silverman SG. Acute necrotizing pancreatitis: role of CT-guided percutaneous catheter drainage. Abdom Imaging 2007;32: Bradley EL, Clements JL, Jr., Gonzalez AC. The natural history of pancreatic pseudocysts: a unified concept of management. Am J Surg 1979;137: Bergman S, Melvin WS. Operative and nonoperative management of pancreatic pseudocysts. Surg Clin North Am

41 급성췌장염진료권고안 : 급성췌장염의국소합병증과괴사성췌장염의치료 ;87: , ix. 61. Cheruvu CV, Clarke MG, Prentice M, Eyre-Brook IA. Conservative treatment as an option in the management of pancreatic pseudocyst. Ann R Coll Surg Engl 2003;85: Nguyen BL, Thompson JS, Edney JA, Bragg LE, Rikkers LF. Influence of the etiology of pancreatitis on the natural history of pancreatic pseudocysts. Am J Surg 1991;162: ; discussion Pitchumoni CS, Agarwal N. Pancreatic pseudocysts. When and how should drainage be performed? Gastroenterol Clin North Am 1999;28: Zerem E, Pavlovic-Calic N, Susic A, Haracic B. Percutaneous management of pancreatic abscesses: long term results in a single center. Eur J Intern Med 2011;22:e50-e Freeny PC, Hauptmann E, Althaus SJ, Traverso LW, Sinanan M. Percutaneous CT-guided catheter drainage of infected acute necrotizing pancreatitis: techniques and results. AJR Am J Roentgenol 1998;170: Heider R, Meyer AA, Galanko JA, Behrns KE. Percutaneous drainage ofpancreatic pseudocysts is associated with a higher failure rate than surgical treatment in unselected patients. Ann Surg 1999;229: ; discussion Soliani P, Franzini C, Ziegler S, et al. Pancreatic pseudocysts following acute pancreatitis: risk factors influencing therapeutic outcomes. JOP 2004;5: Lang EK, Paolini RM, Pottmeyer A. The efficacy of palliative and definitive percutaneous versus surgical drainage of pancreatic abscesses and pseudocysts: a prospective study of 85 patients. South Med J 1991;84: D'Egidio A, Schein M. Percutaneous drainage of pancreatic pseudocysts: a prospective study. World J Surg 1992;16: ; discussion Adams DB, Anderson MC. Changing concepts in the surgical management of pancreatic pseudocysts. Am Surg 1992;58: Nealon WH, Walser E. Main pancreatic ductal anatomy can direct choice of modality for treating pancreatic pseudocysts (surgery versus percutaneous drainage). Ann Surg 2002;235: Baron TH. Endoscopic drainage of pancreatic fluid collections and pancreatic necrosis. Gastrointest Endosc Clin N Am 2003;13: Weckman L, Kylanpaa ML, Puolakkainen P, Halttunen J. Endoscopic treatment of pancreatic pseudocysts. Surg Endosc 2006;20: Gumaste VV, Aron J. Pseudocyst management: endoscopic drainage and other emerging techniques. J Clin Gastroenterol 2010;44: Harewood GC, Wright CA, Baron TH. Impact on patient outcomes of experience in the performance of endoscopic pancreatic fluid collection drainage. Gastrointest Endosc 2003;58: Johnson MD, Walsh RM, Henderson JM, et al. Surgical versus nonsurgical management of pancreatic pseudocysts. J Clin Gastroenterol 2009;43: Varadarajulu S, Christein JD, Tamhane A, Drelichman ER, Wilcox CM. Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos). Gastrointest Endosc 2008;68: Palanivelu C, Senthilkumar K, Madhankumar MV, et al. Management of pancreatic pseudocyst in the era of laparoscopic surgery-experience from a tertiary centre. Surg Endosc 2007;21: vansonnenberg E, Wittich GR, Goodacre BW, Casola G, D'Agostino HB. Percutaneous abscess drainage: update. World J Surg 2001;25: ; discussion Baril NB, Ralls PW, Wren SM, et al. Does an infected peripancreatic fluid collection or abscess mandate operation? Ann Surg 2000;231: Venu RP, Brown RD, Marrero JA, Pastika BJ, Frakes JT. Endoscopic transpapillary drainage of pancreatic abscess: technique and results. Gastrointest Endosc 2000;51: Vitale GC, Davis BR, Vitale M, Tran TC, Clemons R. Natural orifice translumenal endoscopic drainage for pancreatic abscesses. Surg Endosc 2009;23: Lee MJ, Rattner DW, Legemate DA, et al. Acute complicated pancreatitis: redefining the role of interventional radiology. Radiology 1992;183: