대한내과학회지 : 제 89 권제 5 호 2015 http://dx.doi.org/10.3904/kjm.2015.89.5.494 특집 (Special Review) - 췌담도질환의최신지견 급성췌장염의진단및치료 순천향대학교의과대학천안병원내과학교실 이태훈 Diagnosis and Treatment of Acute Pancreatitis Tae Hoon Lee Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea Acute pancreatitis is common, and is sometimes associated with significant morbidity and mortality. Early diagnosis and assessment of the severity of the condition are important when decisions must be made on appropriate early-stage treatment and/or patient transfer to medical facilities familiar with the condition. Initial intensive management of acute pancreatitis is important to minimize complications and mortality. In the present review, we discuss initial diagnosis of the condition, severity assessment, and the adequacy of early treatments, with reference to recently updated Korean guidelines. (Korean J Med 2015;89:494-506) Keywords: Acute pancreatitis; Diagnosis; Severity; Treatment 서론급성췌장염은비교적흔히진료할수있는질환이나중증도가매우다양하여췌장에만염증이발생하는경증의형태에서부터다발장기부전및사망에이르는중증의형태까지발생할수있다. 경증췌장염에서는사망률이 1% 미만인데반해, 중증췌장염에서는매우높아무균괴사췌장염에서는 10%, 감염괴사췌장염의경우는 25-30% 에이른다 [1]. 급성췌장염환자에서사망은약 50% 에서발병 2주내에발생하므로급성췌장염의진단과동시에중증도평가를시행해초기에중증경과를보일것으로예측되는환자를선별하여집중치료를제공하고, 향후적절한치료를제공할수 있는기관으로전원하거나집중치료의기준을제시하는것이중요하다. 또한초기에경증또는중등도의췌장염이라하더라도중증췌장염으로진행할수있기때문에초기집중적인치료가매우중요하다. 이에본고에서는급성췌장염의진단과중증도분류및기본적인치료지침을위주로살펴보고자한다. 급성췌장염의진단급성췌장염발생시정확한진단과원인에대한감별후중등도를파악하여초기에적절한치료계획을세우는것이치료의예후에매우중요하다. 그러나전형적인임상소견이 Correspondence to Tae Hoon Lee, M.D., Ph.D. Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, 31 Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Korea Tel: +82-41-570-3662, Fax: +82-41-574-5762, E-mail: thlee9@schmc.ac.kr Copyright c 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 494 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Tae Hoon Lee. Diagnosis and treatment of acute pancreatitis - 없거나검사결과가모호하거나다른복부질환과의감별이필요하여진단이어려운경우도많다. 진단기준일반적으로급성췌장염은상복부통증, 혈액검사에서혈청아밀라아제나리파아제가정상상한치의 3배이상상승, 영상학적으로복부전산화단층촬영 (abdominal computed tomography, CT), 자기공명영상 (magnetic resonance imaging, MRI), 복부초음파등에서췌장염소견에합당할때, 이세가지중두가지이상만족할경우로진단한다 [1]. 그러나이런진단기준에부합되더라도다른급성복통을일으킬수있는위장관천공, 급성담낭염, 장마비, 장간막동맥허혈혹은경색, 급성대동맥박리, 급성심근경색등에대한감별이반드시필요하다. 임상증상및징후급성췌장염환자의약 90% 이상에서상복부통증을호소하며, 40-70% 에서는등으로방사되는전형적인복통을호소한다. 복통의특징은시작과동시에 30분안에빠르게최고조로이르게되어참기어려울정도의통증을유발하며호전없이 24시간이상지속되기도한다. 복통외에나타나는증상과징후는식욕부진, 오심과구토, 고열, 장음의감소등이있다 [2-4]. 신체검사에서는복부에심한압통이있으면서때때로복부의긴장 (abdominal guarding) 이동반된다. 드물지만모든환자에서복통이나타나는것은아닌데, 특히중증급성췌장염환자의 30-40% 정도에서전형적인복통증세를보이지않아부검으로급성췌장염이진단된경우가있다. 이는복통이없이혼수상태나다발성장기부전으로내원해초기진단이어려웠기때문으로설명된다 [5,6]. 생화학적검사급성췌장염이의심될때혈청의췌장효소상승은진단에중요한역할을한다. 가장흔히이용되는검사는혈청아밀라아제와리파아제검사로리파아제가아밀라아제에비해민감도는비슷하지만특이도는더우월하다 [7]. 혈청아밀라아제의근원은췌장이약 40% 정도를차지하고있고나머지는주로침샘과다른부분에있다. 따라서혈청아밀라아제상승은급성췌장염외에도다른질환들을감별해야한다. 또한급성췌장염이라도상승하지않는경우가있는데, 이는혈청아밀라아제가급성췌장염발생후바로감소하기때문에경한급성췌장염에서혈액검사시기가늦어진경우, 만성 췌장염특히알코올성만성췌장염의급성악화의경우, 중성지방의상승이검사를방해하여고중성지방혈증이있는경우정상수치로나올수있다 [8-10]. 반대로혈청아밀라아제는신부전이있거나 macroamylasemia 같은췌장질환이아닌경우에도상승할수있다. 혈청리파아제는췌장염의진단에있어서아밀라아제보다우수한데민감도는 85-100%, 특이도는 84.7-99% 정도로알려져있다 [11]. 혈청리파아제는아밀라아제에비해더오랫동안수치가상승되어있고특히특이도에있어혈청리파아제는췌장외에는영향을줄다른중요한근원이되는장기가없다. 그러나혈청리파아제역시급성췌장염이외의상태에서도상승할수있는데특히신부전이있을때아밀라아제와마찬가지로신장기능의저하에의해제거기능이감소하여수치가상승하게된다. 크레아티닌청소율이 13-39 ml/min 에서아밀라아제는반수이상, 리파아제는 1/4 정도에서증가되어있다 [12,13]. 다른췌장효소검사로는혈액이나소변으로아밀라아제 isoenzyme, phospholipase A2, elastase1, anionic trypsinogen (trysinogen-2) 등을측정할수있다 [14]. 그러나임상에서흔하게사용되지는않고있다. 영상검사복부초음파검사는비침습적인검사로췌장의비대, 췌장주변의염증변화, 복수등급성췌장염의소견을관찰할수있고원인감별에도움을줄수있어초기검사로추천될수있다 [7]. 그러나복부비만이나주변장관의공기로인해정확한검사를시행하기가어려운경우가적지않아초음파검사의주요목적은급성췌장염의확진보다는담낭담석이나총담관담석에의한총담관의확장을확인하는데있다. 복부 CT는급성췌장염을확진하는데있어가장좋은검사로다른복부질환들을감별할수있고췌장염의중증도를결정할수있으며동반된합병증을확인할수있다 [1,7]. 최근에는 multi-detector CT의사용으로정확도가증가하고있다. 급성췌장염을나타내는복부 CT 소견으로는췌장의비대, 췌장실질의불균질 (heterogeneity), 췌장주변의액체저류등이있으며조영제를사용하면췌장괴사를확인할수있다. 그러나일부연구에서 CT 촬영중에사용하는조영제가췌장의미세순환에영향을주어췌장염을악화시킨다는보고가있다 [15,16]. 또한모든급성췌장염환자에서복부 CT 검사가필요한것은아니므로다른방법으로급성췌장염을진단하거나다른질환을배제하는데문제가없다면증상발생후 72-96시간후에검사하는것이추천된다. 추가로복부 - 495 -
- 대한내과학회지 : 제 89 권제 5 호통권제 663 호 2015 - CT를시행하는경우는환자가장기부전이지속되거나, 패혈증소견을보이거나, 임상적으로악화되는경우등이다 [1]. Magnetic resonance cholangiopancreatography (MRCP) 는담췌관의해부학구조를파악하고담관담석을확인할수있으며조영 MRI로는출혈성췌장괴사를감별하는데 CT보다유용하다. 일반적으로복부 MRI는 CT만큼이나진단에있어정확하고합병증이나췌장의괴사, 증증도평가에도좋은검사이다 [7,17,18]. 내시경역행담췌관조영술 (Endoscopic retrograde cholangiopancreatography, ERCP) 은시술과관련된합병증으로인해급성췌장염의진단을목적으로시행하지않으나담석성췌장염이강력히의심되는경우에는진단과동시에치료목적으로고려해야한다. 원인에대한평가및감별진단급성췌장염의원인에대한평가를위해이전췌장염병력, 담석질환, 음주력, 약물복용력, 고지혈증유무, 외상, 최근 ERCP와같은침습적시술여부등과같은개인력과췌장질환의가족력, 신체검진, 혈청생화학검사, 영상검사등을시 행해야한다 (Table 1). 혈액검사로빌리루빈, ALT, AST, 알칼리인산분해요소 (alkaline phosphatase) 등을측정하여담석성췌장염을감별해야한다. ALT 가 150 IU/L 이상인경우나빌리루빈, 알칼리인산분해요소, γ-gtp, ALT, ALT/AST 중에 3개이상증가된경우도담석성급성췌장염일가능성이높다 [19,20]. 중성지방이 1,000 mg/dl 이상증가한경우에는고지혈증에의한췌장염가능성이높으며, 고칼슘혈증이있으면부갑상선기능항진증도고려해야한다 [21,22]. 영상검사로는비교적손쉽게시행할수있는복부초음파가담낭담석이나담도확장등을확인하여원인을아는데도움을줄수있다. 그러나복부초음파에이상이없다고담석성췌장염을배제하기는어렵다. 복부 CT는진단과동시에종양이나외상등여러가지원인에대해평가할수있지만, 담관담석의확인은민감도가 40-53% 정도로낮아서적당하지않다 [20]. 담도성원인에대한감별로복부초음파나생화학검사에서음성이고급성췌장염의원인이불확실한경우미세담석이나만성췌장염, 종양등감별을위해내시경초음파 (endoscopic ultrasonography) 가추천된다. 내시경초음파역시음성소견이 Table 1. Various 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 dysfunction of 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 (sicca syndrome, primary sclerosing cholangitis, autoimmune hepatitis, celiac disease) Genetic (familial, sporadic) Idiopathic SOD, sphincter of Oddi; ERCP, endoscopic retrograde cholangiopancreatography. - 496 -
- 이태훈. 급성췌장염의진단및치료 - 면 MRCP 가담관담석뿐아니라해부학적변이여부등을판별하는데도움을줄수있다. 여기에서도정상이라면유전적원인에대한검사도고려해보아야한다. 급성췌장염의중등도평가급성췌장염으로사망하는경우약 50% 에서발병 2주내에발생하므로급성췌장염의중증도평가는초기에중증경과를보일것으로예측되는환자를선별하여조기에집중치료를시작하고예후를예측하는데중요하다. 그러나급성췌장염의임상양상은다양하여중증도에대한객관적인평가는쉽지않아서현재까지중증췌장염의예측은각나라나기구마다여러판정기준이이용되고있다. 임상지표로서신체질량지수 (Body Mass Index, BMI) 30 kg/m 2 이상인비만이중증급성췌장염과관련이있는것으로알려져있다. 그러나비만이급성췌장염과관련된사망에는관련이없다는보고도있다 [23,24]. C-reactive protein (CRP) 수치는급성췌장염악화를제시하는믿을만한인자로현재여겨지고있다. 여러권고안들에서도급성췌장염발생 48시간이후측정한 15 mg/dl 이상의혈청 CRP 수치를예후인자로추천하고있다 [1,3,7,25]. 다른생화학검사로입원시혈청 blood urea nitrogen (BUN) 20 mg/dl과입원 24시간이후 BUN 상승이사망률과연관성을가진다는보고가있고 [26], 입원시와입원 24시간이내의혈청 creatinine > 2.0 mg/dl 이높은사망률과관련이있다는보고가있었다 [27,28]. 급성췌장염에서혈당 > 250 mg/dl인경우높은사망률과관련을가진다는보고도있지만, 혈당 > 125 mg/dl는장기부전이나사망률과는연관성이떨어진다는보고도있다 [29,30]. 급성췌장염환자에서혈관내용적의감소로인한적혈구용적률 (hematocrit) 의상승과관련되어입원시적혈구용적률 44% 이거나입원후 24시간이내에적혈구용적률이감소되지않는경우는췌장의괴사와연관된예측인자로제시되었다 [31]. 췌장효소활성펩타이드, 특히 trypsinogen activation peptide 와 carboxypeptidase activation peptide 측정은급성췌장염의중증도예측에중요한정보를제공하지만혈청 CRP 이외에는신속검사가어려워임상적유용성은떨어진다 [3]. 영상검사를이용한중증도평가급성췌장염에서췌장의허혈, 괴사및병변범위를평가하기위해조영증강복부 CT가필수적이고괴사성췌장염과부종성췌장염을구별하는데가장유용한검사이다. 또한 복부 CT에서확인된췌장의괴사는국소및전신합병증과밀접한연관성이있는것으로알려져있어췌장의괴사가의심되는경우에적절한검사이다. 급성췌장염발병 4-10일후시행하면거의 100% 에서췌장괴사의진단이가능하고입원초기 ( 입원후 36-48시간이내 ) 에시행하여도급성췌장염의중증도평가에유용하다 [1,3,7]. CT severity index 는췌장괴사의유무, 괴사범위및염증변화의범위등을결합하여수치화한것으로 (Table 2) 예후와잘연관되어있는것으로받아들여지고있다 [32]. CT severity index가 0-3인경증급성췌장염환자는임상양상이악화되는경우에만복부 CT를추가로시행하고, CT severity index가 4-10인중등도이상의급성췌장염환자에서는임상상의호전이없는경우에도시행할수있다. CT를재시행하는경우는임상호전이없거나증상의변화혹은침습적인시술을고려하는경우등이다 [1]. 또한, 급성췌장염이회복되어퇴원하는경우에도가성낭종이나가성동맥류와같은무증상합병증을발견하기위해복부 CT 시행이권고되기도한다 [33]. 조영증강복부 MRI Table 2. Computed tomography (CT) grading of severity CT grade (A) Normal pancreas 0 (B) Oedematous pancreatitis 1 (C) B plus mild extrapancreatic changes 2 (D) Severe extrapancreatic changes including 3 one fluid collection (E) Multiple or extensive extrapancreatic 4 collections Necrosis None 0 < One third 2 One third-one half 4 > Half 6 CT severity index = CT grade + necrosis score Complications 0-3 8% 4-6 35% 7-10 92% Deaths 0-3 3% 4-6 6% 7-10 17% Modified from the World Association guidelines and based on Balthazar and colleagues. - 497 -
- The Korean Journal of Medicine: Vol. 89, No. 5, 2015 - 도조영증강복부 CT와유사한정도로췌장괴사의유무, 괴사및염증성변화의범위등을평가하는데유용하다. 중증도판정지표를이용한평가 단일생화학검사나영상검사만으로는중증도평가에한계가있어다양한지표들을활용해중증도를판정하는데이용되고있다. 1974년발표된 Ranson 지표는다변수평가법 Table 3. Ranson criteria for the prediction of severity of acute pancreatitis On admission Age > 55 yr (> 70 yr) White cell count > 16,000/mm 3 (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 hr Decrease in hematocrit by 10% (same) Blood urea nitrogen increases by > 5 mg/dl (> 2 mg/dl) Calcium < 8 mg/dl (same) PaO 2 < 60 mmhg (omitted) Base deficit > 4 meq/l (> 6 meq/l) Fluid sequestration > 6 L (> 4 L) 중가장많이알려진것으로입원시에 5개항목, 입원후 48 시간이내에 6개항목을측정하여 3가지이상관찰되는경우중증췌장염으로정의하였다 (Table 3) [34]. Imrie 등 [35] 이개발한 Glasgow 지표는알코올과담석췌장염에모두사용할수있는 Ranson 지표와유사한다변수평가법으로, Ranson 지표중 3개지표를삭제하고알부민을첨가하여총 9개의지표로단순화하였다 (Table 4). Acute Physiology and Chronic Health Evaluation (APACHE) II 지표는특정질환에대한임상평가가아니라중환자실에서이용되어온지표로 12가지의생리적인측정치와나이, 5개의장기에기초한만성건강상태를평가하고이를점수화하여전체점수를합산하는방 Table 4. Glasgow severity scoring system for acute pancreatitis Age > 55 yr White cell count > 15,000 /mm 3 PaO 2 < 60 mmhg Serum lactate dehydrogenase > 600 U/L Serum aspartate aminotransferase > 200 U/L Serum albumin < 3.2 g/dl Serum calcium < 8 mg/dl Serum glucose > 180 mg/dl Serum urea > 45 mg/dl Table 5. APACHE II scoring system Physiological parameter +4 +3 +2 +1 0 +1 +2 +3 +4 Temperature, rectum, 41 39-40.9 38.5-38.9 36-38.4 34-35.9 32-33.9 30-31.9 29.9 Mean arterial pressure, mmhg 160 130-159 110-129 70-109 50-69 49 Heart rate, n/min 180 140-179 110-139 70-109 55-69 40-54 39 Respiration rate, n/min 50 35-49 12-24 10-11 6-9 5 Oxygenation, mmhg 25-34 FiO 2 > 0.5, A-a DO 2 500 350-499 200-349 < 200 FiO 2 < 0.5, PO 2 > 70 61-70 55-60 < 55 Arterial ph 7.7 7.6-7.69 7.33-7.49 7.25-7.32 7.15-7.24 < 7.15 Serum sodium, mmol/l 180 160-179 155-159 7.5-7.59 130-149 120-129 111-119 110 Serum potassium, mmol/l 7 6-6.9 150-154 3.5-5.4 3-3.4 2.5-2.9 < 2.5 Serum creatinine, mg/dl (Duplication in acute renal failure) 3.5 2-3.4 1.5-1.9 5.5-5.9 0.6-1.4 < 0.6 Hematocrit, % 60 50-59.9 30-45.9 20-29.9 < 20 White cell blood count, 10 3 /mm 40 20-39.9 46-49.9 3-14.9 1-2.9 < 1 15 minus Glasgow coma scale score 15-19.9 In these 12 parameters must be added the age (yr) [< 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). APACHE, acute physiology and chronic health evaluation. - 498 -
- Tae Hoon Lee. Diagnosis and treatment of acute pancreatitis - 법으로산출된다 (Table 5) [36]. APACHE II 지표는입원수시간내에급성췌장염의중증도를판정할수있고수시로반복측정할수있어진행여부를평가할수있다는장점이있다. 비만이중증급성췌장염의발병과관련이있고사망의독립적인예측인자로인식되면서 APACHE II 지표에신체질량지수를더하여새로운 APACHE-O도만들어졌다 [37]. New Japanese severity scoring system 은 9개의예후인자로단순화해중증과경증췌장염을쉽게구별하였다 (Table 6) [38]. Bedside index for severity in acute pancreatitis 지표는입원 24 시간동안 BUN > 25 mg/dl, impaired mental status, systemic inflammatory response syndrome (SIRS), age > 60 years, pleural effusion 5개항목을갖고각각 1점을주어점수가높아짐에따라사망률이높아짐을보고하였다 (Table 7) [39]. 최근의 the international association of pancreatology (IAP)/the american pancreatic association (APA) 가이드라인에따르면증증급성췌장염의예측에중요한것으로입원당시와 48시간후 SIRS 가제시되고있다 [1]. SIRS는다음네가지기준중 2가지이상만족할때로정의한다. (1) temperature < 36 (96.8 ) or > 38 (100.4 ), (2) heart rate > 90/min, (3) respiratory rate > 20/min, and (4) white blood cells (< 4 10 9 /L, > 12 10 9 ) or 10% bands [40]. 급성췌장염에서 48시간이상지속되는 SIRS는다발성장기부전및사망률과관련있는중요한요소이다. 지속적인 SIRS 시사망률이약 25% 이르는반면일시적인 SIRS는 8% 정도로보고되었고민감도는 79-86%, 특 Table 6. The new Japanese criteria for grading severity of acute pancreatitis Prognostic factor BE -3 meq/l or shock PaO 2 60 mmhg (room air) or respiratory failure BUN 40 mg/dl or creatinine 2.0 mg/dl LDH two folds of upper normal limit Platelet count 1 10 5 /mm 3 Ca 7.5 mg/dl CRP 15 mg/dl SIRS score 3 Age 70 yr Sum of the points for the positive prognostic factor is defined as the new Japanese severity score (new JSS); Severe acute pancreatitis is defined as new JSS 3 points; Mild acute pancreatitis is defined as new JSS 2 points. BE, base excess; CRP, C-reactive protein; SIRS, systemic inflammatory response syndrome. 이도 79-86% 였다 [41,42]. SIRS 는비교적간단하고반복적으로측정할수있어다른복잡한 scoring 시스템에비해유용하다할수있다. 그러나다른검사방법보다 SIRS가더우수하거나열등한지는명확하지는않다 [43]. 결국환자자체의위험요소 ( 나이, 동반질환, BMI 등 ) 와 SIRS의지속여부같은임상적위험도분류, 초기치료에대한반응 ( 지속적인 SIRS 여부, BUN, Creatinine 등 ) 이급성췌장염의예후를예측하는중요한기준이된다 [1]. 급성췌장염의치료 급성췌장염진단및중등도예측후초기집중치료를요하는환자군을선별하여적절한치료를시행하는것은췌장염에의한합병증발생및사망률을감소시키는데중요하다. 급성췌장염자체를호전시키는방법은아직뚜렷하지않아주로보존적치료와합병증에대한처치가치료의근간으로환자를금식시키고적절한수액공급을조기에실시하는것이가장중요하다. 이외에도진통제를포함한보존적치료, 경장관영양법, 합병증을줄이기위한항생제및단백분해효소등의사용여부등으로분류해볼수있다. 보존적치료 수액요법급성췌장염발생시혈관투과성의증가와 colloid 삼투압의감소로인해췌장주위, 후복막강뿐아니라복강, 흉강등 Table 7. BISAP 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: Temperature of < 36 or > 38 Respiratory rate > 20 breaths/min or PaCO 2 < 32 mmhg Pulse > 90 beats/min WBC < 4,000 or > 12,000 cells/mm 3 or > 10% immature bands Age > 60 yr 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. BISAP, bedside index for severity in acute pancreatitis; SIRS, systemic inflammatory response syndrome; WBC, white cell blood count. - 499 -
- 대한내과학회지 : 제 89 권제 5 호통권제 663 호 2015 - 으로세포외액의누출이발생해상당한순환혈장량의손실이유발된다. 저혈량증 (hypovolemia) 은췌장의미세순환을감소시켜괴사성췌장염발생의주요원인이된다. 따라서심혈관장애를안정화하고췌장의미세순환을증가시키기위해손실된수액에대한즉각적인공급이필요하다. 초기수액투여는일반적으로 Ringer s lactate 가추천되고, Hartmann s solution 이이와성분이유사하다. 초기수액공급의기준은심혈관및신기능유지를목적으로평균혈압 65 mmhg 이상, 소변량 > 0.5-1 ml/kg/hr를유지할것을권고한다 [2,3,25,44-46]. 초기에 5-10 ml/kg/h 속도로투여하고일반적으로첫 24시간에 2,500-4,000 ml 정도면충분하다고한다. 모든췌장염환자에서 4,000 ml 이상의과도한수액공급이필요하지는않다. 2015년일본지침의경우탈수나 shock이있는경우주의깊은모니터링을하면서 150-600 ml/h 로초기수액공급하고, 탈수가없는경우 130-150 ml/h 로투여할것을권고한다 [7]. 일반적으로중심정맥압측정은필요하지않으나중증의췌장염에서는적절한용적상태파악을위해필요하고, 폐동맥쐐기압 (pulmonary wedge pressure), 동맥가스혈분석, 전해질검사등을시행해야한다 [2,3,25,44-46]. 또한, 적절한수액공급의지표로활력징후, 소변량및헤마토크릿의감소정도 ( 입원후첫 12시간, 24시간 ) 를적어도매 4-6시간간격으로측정해야한다. 대부분의시험적연구에서초기의적극적인수액공급및산소공급은췌장괴사를최소화하고생존율을증가시킨다고보고하고있다 [47-49]. 그러나최근몇몇연구결과에서는초기 24시간이내에 4 L 이상의과도한수액공급이모든환자에서필요하지는않으며초기에과도한수액공급으로인한혈액희석 (hemodilution) 으로호흡기합병증이증가하거나패혈증및사망률빈도가높아진다는보고도있다 [50-52]. 통증조절과산소공급급성췌장염에의한통증은지속적이고심해불안감을야기하고임상경과에악영향을미칠수있어마약성진통제등을이용한복통의완화는치료초기에매우중요하다. 현재까지는어떤특정한형태의투약에대한명확한이점이보고된바없으나일부연구에서 non-narcotic analgesic buprenorphine이 procaine보다우수하며오디괄약근수축과같은악영향을미치지않고 pethidine (meperidine hydrochloride; Demerol) 과비슷한진통효과가있다고한다 [53-55]. 또한복통이심할경우환자주도통증조절 (patient-controlled analgesia) 을시행해볼수있다. 진통제투약의빈도나양은경험있는 의사에의해모니터링되어야하며동시에침상에서산소포화도모니터링을시행해야한다. 산소공급은첫 24-48시간동안투여를권고하는데, 특히통증등으로마약성진통제를사용하는경우에는초기에침상에서산소포화도모니터링을하면서공급한다. 산소농도는적어도 95% 이상유지되어야하며 95% 이하인경우동맥가스혈분석을시행한다 [2,3,25,44-46]. 경비위배액경비위배액 (nasogastric drainage) 은경증의급성췌장염에서는필요하지않으나마비성장폐쇄 (paralytic ileus) 나잦은구토등이있는경우필요할수있다. 그러나급성췌장염환자에서경비위배액이췌장의안정화에유용하다는뚜렷한연구결과는없다. 경증및중등도췌장염의무작위대조군연구에서위배액은통증경감이나입원기간단축등의임상경과에의미있는영향을주지못했다. 오히려통증이나구역감을증가시킨다는보고들도있다. 따라서모든췌장염에서경비배액관삽입은권고되지않으며췌장염으로인한마비성장폐쇄나잦은구토가있는경우삽입을고려해야한다 [2,3,25, 44-46]. 영양지원경증의급성췌장염에서자연적인식이진행은대부분 3-7 일내가능하므로비경구영양법이나경장관영양법 (enteral nutrition) 이필요하지는않다. 일반적으로경증의췌장염에서환자는통증이없어지면짧은기간금식후경구식이가가능하고통증이없으면가능한빨리경구식이를진행하는것이좋다. 따라서경증의췌장염에서는환자가 5-7일이내에정상식이를섭취할수있다면경장관영양등은일반적으로필요하지않다 [2,3,25,44-46]. 경장관영양법은중증의급성췌장염초기에장마비등이없다면조기에시작하는것이경정맥영양법 (intravenous hyperalimentation) 보다우수하다. 경장관영양법은염증성반응을제거하고감염빈도나수술빈도를낮추고입원기간을단축해비용도절감할수있다고보고되었다. 그러나사망률이나감염외다른합병증의발생빈도에는별다른차이가없었다. 영양공급은대부분경장관영양만으로가능하나충분한칼로리공급이어렵다면경정맥영양이추가로필요할수있다. 경장관영양법이보다우수하다고판단되는근거는중증의급성췌장염에서장관의장벽기능 (barrier function) 이저하되면박테리아나 endotoxin의장벽투과성을증가시켜장기부전을일으킬수있는 nitric oxide 나 cytokine의생성을촉진시킬수있고, 또한패혈성합병증을일으킬수있는강력한병적장내세균의위내군체형성 - 500 -
- 이태훈. 급성췌장염의진단및치료 - (colonization) 빈도를증가시킬수있기때문이다. 경장관영양법은이러한장벽기능을안정화시켜적절한영양공급뿐아니라전신합병증을예방하고이환율및사망률을감소시킬수있다. 또한경정맥영양과관련된감염, 패혈증같은합병증역시피할수있다. 그러나최근의메타분석결과를보면경장관영양이우수하다는결과와함께안정성이나효과에서경장관영양법이더우수하다고보기에는자료가충분치않다는의견도있다 [56,57]. 영양공급로는경비공장배액관 (nasojejunal tube) 이일반적으로추천되었었다. 일반적으로췌장외분비기능의자극을피하기위해가능한 treitz ligament 이하로공장배액관 (jejunal tube) 을삽입해영양공급하는것을추천한다 [2,3,25,44-46]. 그러나최근의문헌고찰에따르면경비위배액관 (nasogastric tube) 을이용한영양공급이공장배액관을이용하는것과비교해안전성이나사망률등에차이가없고, 또한경비위배액관은삽입이비교적쉽고관을유치하기도용이하다 [58,59]. 따라서경비관삽입은환자상태등에따라선택적으로결정될수있으며현재는두가지방법모두추천된다 [1]. 비경구영양법은인체에서췌장의분비기능을유의하게자극하지않고췌장기능에도특별한부작용을일으키지는않는다. 비경구영양법의적응증은비교적단순해지속적인장마비나 complex pancreatic fistulae, 복부구획증후군등으로인해경장관영양이불가능한경우, 즉경장관영양으로목적한만큼의영양섭취가어려운경우이다 [2,3,25,44-46]. 경구식이는탄수화물과단백질이충분하고지방이전체에너지섭취의 30% 미만의저지방식이가추천된다 [60]. 예방적항생제투여단순히급성췌장염에서감염성합병증의예방을위한항생제사용은추천되지않는다 [1]. 그러나감염성췌장괴사나패혈증환자에서의사망률은매우높기때문에중증의급성췌장염에서감염성합병증을예방하기위해항생제사용이추천되었다. 일반적으로괴사성췌장염에서발열, 백혈구증가증이나장기부전이동반된경우배양검사나복부 CT 유도하흡입검사등을시행하는동안에예방적으로항생제를사용하는것이합당하다. 이는임상증상이없는괴사성췌장염에서예방적항생제사용이내성균이나진균감염의기회를제공할수있다는데근거한다. 최근의무작위대조군연구결과를보면췌장침투율이좋은 ciprofloxacin, ofloxacin, imipenem, pefloxacine (pefloxacin) 같은항생제를예방적투여시췌장내충분한조직농도를유지할수있어감염성합 병증의빈도를낮추고일부연구에서는사망률을감소시킨다는보고가있다. 그렇지만사망률이나합병증감소에차이가없었다는보고들도있다. 메타분석에서도췌장침투율이좋은광범위항생제의예방적사용은감염성합병증이나사망률을감소시킨다고보고하였으나역시차이가없다는보고들도있다 [61-66]. 따라서향후이에대한명확한진단기준에따른광범위한대단위비교연구가필요하다. 또한, 예방적광범위항생제의사용시중증의급성췌장염에서감염성합병증이나사망률을감소시킨다하더라도내성균이나진균감염의위험을증가시키고이로인한사망률을증가시킬수있다는것을고려해야한다 [62-72]. 임상연구에서는예방적으로췌장조직침투율이좋은 fluconazole의사용이중증의급성췌장염에서진균감염의빈도를감소시킨다고보고한바있으나이에대한대조연구는아직보고된바없다 [71-72]. 결과적으로중증의췌장염혹은중증췌장염이예측되는환자에서감염과연관된합병증빈도감소를목적으로광범위항생제의예방적투여는근거가미약하고사망률을감소시키거나 CT로증명된괴사성췌장염에서의생존율도증가시키지는않는다. 궤사성췌장염에서감염이의심되거나추가적인시술이필요한경우에는항생제를투여한다 [1]. 약물치료 : 단백분해효소억제제제등단백분해효소억제제 (Protease inhibitor) 나췌장분비억제제 (anti-secretory), 항산화제혹은항염증제 (anti-oxidative, anti-inflammatory agent) 등의효과에대해서는논란이되고있다. 지금까지의초기연구에서단백분해효소억제제나췌장분비억제제 (octreotide), 항염증제 (lexipafant) 등의유용성이제기되었으나뚜렷하게우수하다는연구결과를보여주지는못했다. 특히급성췌장염에서단백분해효소억제제의유용성은대부분의초기연구에서는실망스런결과를보여주었고일련의무작위대조군연구 (6 trials of gabexate mesilate and 4 trials of aprotinin) 의메타분석에따르면급성췌장염에서단백분해효소억제제의사용이합병증을감소시키나수술적중재술의빈도나사망률을감소시키지는않는다고보고하였다 [73-76]. 그러나중등도이상의급성췌장염에서는사망률이유의하게감소하였다. 또한, 고용량 gabexate mesilate (2,400 mg/day) 의지속정맥주입이장기부전을동반한중증췌장염에서합병증과사망률을감소시켰다는보고도있다 [77]. 췌장효소분비를억제하는작용이있는 somatostatin이나이와유사한 octreotide 역시급성췌장염초기에사용하면췌장염 - 501 -
- The Korean Journal of Medicine: Vol. 89, No. 5, 2015 - 에의한합병증이나사망률을감소시킬수있다는연구보고도있지만상반된보고도있다. 이러한연구에대한메타분석에서는 somatostatin이나 octreotide 같은약물이급성췌장염에서사망률을감소시킬수있다고하였다 [78]. 일본이나이탈리아등의가이드라인에서는중등도이상의췌장염초기에단백분해효소억제제의정맥주입치료를권고하고있고, 특히일본의경우 gabexate mesilate, nafamostat mesilate, ulinastatin 등의제재에대해중등도에따른구체적인사용지침을제시하기도한다 [45,46,79]. 그러나영국, 미국등의대부분가이드라인에서는메타분석등을근거로현재치료지침으로인정하고있지않다. 따라서향후지역, 인종및중등도에따른국내외대단위비교연구가필요할것으로생각된다. 기타일반적으로 H2-blocker나 proton pump inhibitor (PPI) 는급성췌장염환자에서급성위점막병변 (acute gastric mucosal lesion) 이나출혈성궤양을동반한경우를제외하고는필요하지않다 [2,3,25,44-46]. PPI 사용효과에대한무작위비교연구는아직없고이에대한지침역시아직보고된바없으나스트레스성궤양이나급성위점막병변이발생한급성췌장염의경우사용을고려한다. 한문헌고찰에서는 cimetidine이급성췌장염과연관된합병증의빈도를증가시키는경향이있고통증기간을증가시킬수도있다고보고하고있다 [80]. 그렇지만현재까지 cimetidine이나 H2-blocker, PPI 등이급성췌장염의임상경과를호전혹은악화시킬수있다는임상적근거는부족하다. 장의오염제거 (gut decontamination) 는감염성합병증예방에이점이있다고생각되나아직근거가미약하고 probiotics 의예방적사용역시예방목적으로추천되지는않는다 [1]. 집중치료 (intensive care unit) 및전문가에전원이필요한경우 2013년 IAP/APA 권고안에따르면중증췌장염환자나방사선, 내시경혹은수술적중재술이필요한경우가능한상급병원전문가에의뢰할것을권고한다. 또한급성췌장염환자에서 Society of Critical Care Medicine (SCCM) [81] 기준에한가지이상해당하는경우중환자실집중치료를시행해야한다 [ (1) 분당맥박수 < 40회혹은 > 150회 ; (2) 수축기동맥혈압 < 80 mmhg 혹은평균동맥혈압 < 60 mmhg 혹은이완기동맥혈압 > 120 mmhg; (3) 분당호흡수 > 35회 ; (4) 혈청 sodium < 110 mmol/l or > 170 mmol/l; (5) 혈청 potassium < 2.0 mmol/l or > 7.0 mmol/l; (6) pao 2 < 50 mmhg; (7) ph < 7.1 or > 7.7; (8) 혈당 > 800 mg/dl (> 44.4 mmol/l); (9) 혈청 calcium > 15 mg/dl (> 3.75 mmol/l); (10) 무뇨증, 혹은 (11) 혼수상태 ]. 초기치료에도지속적인장기부전이있는경우역시중환자실집중치료가필요하다 [1]. 담석성췌장염에서담낭절제술의필요성과시기담석성췌장염에서내시경유두괄약근절개술은췌장염의재발을예방할수는있으나근본적으로담낭담석에의한담도성산통이나담낭염을예방할수는없으므로담석성췌장염의경우담낭절제술이필요하다. 담낭절제술은일반적으로경증의췌장염의경우입원해있는동안수술을권고하나중증의췌장염으로췌장주위체액고임등이있는경우는췌장염이회복되거나 6주이상지나시행하는것이안전하다 [1]. 한후향연구에서중증의췌장염에서조기에담낭절제술을시행한경우감염성체액저류 (infected collections) 의빈도가높다고하였다 [82]. 복부구획증후군 (abdominal compartment syndrome, ACS) 의치료 ACS는지속적으로복강내압이 20 mmhg 을초과해상승이지속되는경우로새로운장기부전의발생및악화, 과도한수액투여등과연관이있다. 복압이상승함에따라심박출량이감소하고주요장기로의혈액공급에장애가발생해 ACS 발생은사망률을급격히증가시킬수있다. 일반적인신체검사로진단할수없고방광을통해압력을측정해야한다 [83]. 과도한수액공급, 중증도의췌장염, 신장및호흡기장기부전, CT 등에서여러곳에액체집적이관찰되는경우에는복강내압을주기적으로측정해야한다. 복강내압이 12 mmhg 이상지속시적극적으로복강내감압을위해비위관을삽입해위장감압과적절한수액공급및순환을유지해보존적치료를유지하면서 15 mmhg 이하로유지해야한다. 보존적치료에도 20 mmhg 이상유지되고장기부전이발생하면수술적감압을고려해야한다 [1]. 궤사성췌장염에대한치료무균궤사성췌장염 (sterile necrotizing pancreatitis) 에서방사선, 내시경혹은수술적중재술이필요한경우는 walledoff necrosis에의한종괴로위장이나담도폐쇄가발생하거나감염의증후가없더라도복통같은임상증상이지속되거나 disconnected duct syndrome 등이발생하는경우이다. 괴사성 - 502 -
- Tae Hoon Lee. Diagnosis and treatment of acute pancreatitis - 췌장염에서 2차감염은보통증상발현약 2-4주후에주로발생하는데복부영상에서췌장괴사부위에공기음영이관찰되면강력하게감염을의심할수있고, 괴사조직이나주위저류액의균동정으로감염을증명할수있다. 균감염은복부 CT 또는초음파유도하세침흡인 (fine needle aspiration, FNA) 을통하여진단될수있고, 진단정확도는 89-100% 로높지만위음성률도 12-25% 정도로보고되고있다 [84,85]. 일반적으로는지속적인발열이나염증을나타내는생화학검사수치의증가나영상소견에서감염을예측할수있으므로일반적인사용은추천되지않는다. FNA 는궤사성췌장염발생이후수주간치료에도이차감염의증거가없으면서임상적인호전이없는경우고려함이적절하다. FNA 를시행함으로써감염성궤사의진단을더빨리할수있다거나항생제치료방향이나결과를향상시킬수있다는증거가아직없다 [1]. 감염성췌장괴사가의심되거나확진된경우의치료는괴사된췌장이나췌장주위조직을제거하는것이기본적인방법이나적절한시기는췌장염발생후적어도 4주정도연기하는것이사망률과합병증을줄일수있다 [21,86]. 수술의높은사망률과이환율을극복하기위해서여러가지중재적치료, 즉내시경초음파를이용한경벽배액술 (EUS-guided transmural drainage) 이나경피적배액술을먼저고려하고다음단계로필요하다면내시경혹은수술적궤사제거술을시행한다. 즉감염성췌장괴사환자에서초기에는항생제투여와보존적치료를하여괴사제거술을가능하면최대한지연하고임상적상황이악화되거나패혈증으로진행하는소견이보이면괴사부위의배액술과괴사제거술을시행한다. 급성췌장염발병후 4주정도가지나면정상췌장과괴사된췌장의경계구분이분명해지고괴사부분이액화되므로 (walled-off necrosis) 괴사제거술이용이하고괴사제거술의합병증을최소화할수있다 [1]. 결론급성췌장염은초기에임상증상및생화학검사, 영상검사등을통해진단하고원인감별을시행하며중증도를판정해야한다. 이후중증도에따라적극적인수액치료및통증조절을시행하면서경장관영양법시행여부를결정하고, 항생제나췌장단백효소억제제등의투여여부를결정해야한다. 또한중증췌장염에서는중환자실집중치료및상급병원전원여부에대한평가가고려되어야한다. 복부구획증후 군이나췌장궤사와같은경우사망률과합병증위험이높아내시경치료나방사선중재술, 외과적수술등이필요할수있어적절한치료시기및방법의선택이중요하다. 마지막으로국내에서는아직국내현실을반영한대규모연구결과가부족해대부분외국의연구결과를바탕으로하고있어향후이에대한지속적인연구가요구된다. 중심단어 : 급성췌장염 ; 진단 ; 중증도 ; 치료 감사의글 급성췌장염진료권고안개발에함께참여하시고본원고에도움을주신김태현, 이상협, 고동희교수님께깊이감사드립니다. REFERENCES 1. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology 2013;13(4 Suppl 2):e1-e15. 2. Banks PA, Freeman ML; the Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol 2006;101: 2379-2400. 3. Working Party of the British Society of Gastroenterology, Association of Surgeons of Great Britain and Ireland, Pancreatic Society of Great Britain and Ireland, Association of Upper GI Surgeons of Great Britain and Ireland. UK guidelines for the management of acute pancreatitis. Gut 2005;54 Suppl 3:iii1-iii9. 4. Malfertheiner P, Kemmer TP. Clinical picture and diagnosis of acute pancreatitis. Hepatogastroenterology 1991;38:97-100. 5. Forsmark CE, Baillie J; AGA Institute Clinical Practice and Economics Committee; AGA Institute Governing Board. AGA Institute technical review on acute pancreatitis. Gastroenterology 2007;132:2022-44. 6. Read G, Braganza JM, Howat HT. Pancreatitis--a retrospective study. Gut 1976;17:945-952. 7. Yokoe M, Takada T, Mayumi T, et al. Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015. J Hepatobiliary Pancreat Sci 2015;22:405-432. 8. Clavien PA, Robert J, Meyer P, et al. Acute pancreatitis and normoamylasemia. Not an uncommon combination. Ann Surg 1989;210:614-620. 9. Eckfeldt JH, Kolars JC, Elson MK, Shafer RB, Levitt MD. Serum tests for pancreatitis in patients with abdominal pain. - 503 -
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