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Essentials of Primary Care: 소화기 급성및만성췌장염합병증. 어떻게치료하고추적관찰하여야하는가? 중앙대학교의과대학내과학교실 도재혁 서론최근비만인구가늘어나는것과함께급성췌장염의가장많은원인인담석발생위험이증가하면서급성췌장염의발생빈도도증가하고있다. 1 급성췌장염의중증도 (severity) 는장기부전 (organ failure) 의발생유무와지속기간그리고국소합병증의발생유무에따라경증 (mild), 중등도중증 (moderately severe), 중증 (severe) 구분된다. 급성췌장염의합병증은전신합병증과국소합병증으로구분된다. 전신합병증은호흡계, 순환계그리고신장부전이발생하였거나기존에가지고있던질병이급성췌장염으로인해악화되는경우로정의한다. 국소합병증은췌장주위액체고임 (fluid collection) 이발생한경우나감염의여부와관계없이췌장조직또는췌장주위조직의괴사가발생한경우또는대장괴사, 비장정맥혈전, 문맥혈전, 위배출기능이상이발생한경우로정의한다. 2 전반적인급성췌장염의사망률은약 3-5% 정도이나급성췌장염의약 10-20% 를차지하는중증급성췌장염인경우사망률이 20% 정도로매우높다. 3 그러므로초기집중치료와합병증에대한적절한치료는급성췌장염에의한 사망을줄이는데중요하다. 만성췌장염의중요합병증으로는복통, 췌장효소분비장애따른외분비기능부전, 그리고췌장실질의손상에의한내분비기능부전과이에따른당뇨병등이있다. 본고에서는급성췌장염의일반적인치료원칙과국소합병증발생에따른치료에대해기술하고만성췌장염의합병증에대한치료와추적에대해살펴보고자한다. 급성췌장염 1. 진단과분류급성췌장염은등으로방사되는심한상복부통증, 혈청아밀라제또는리파제수치가정상상한보다 3배이상증가, 영상의학적검사에서췌장의염증이증명되는등 3가지중 2가지이상만족하면진단할수있다. 형태학적으로급성췌장염은췌장실시또는췌장주위조직의괴사 (necrosis) 유무에따라간질성부종성췌장염 (interstitial edematous pancreatitis) 과괴사성췌장염 (necrotizing pancreatitis) 으로분류한다. 일반적으로장기부전은 modified Marshall scoring system (Table 1) 을이용하여 2점이상인경우로정의한다. 급성췌장염의중증도는장 Table 1. Modified Marshall scoring system Score Organ system 0 1 2 3 4 Respiratory (PaO2/FiO2) >400 301-400 201-300 101-200 101 Renal (serum Creatinine) <1.4 1.4-1.8 1.9-3.6 3.6-4.9 >4.9 Cardivascular(Systolic BP, mmhg) >90 <90, Fluid response <90, Not fluid response <90, ph<7.3 <90, ph<7.2 Oxygen (L/min) FiO2 Room air 21 2 25 4 30 6-8 40 9-10 50-120 -

- 도재혁. 급성및만성췌장염합병증. 어떻게치료하고추적관찰하여야하는가? - Table 2. Degree of severity of acute pancreatitis Mild acute pancreatitis Lack of organ failure and local/systemic complications Moderately severe acute pancreatitis transit organ failure* organ failure that resolves within 48 hours and/or local or systemic complications Severe acute pancreatitis persistent single or multiple organ failure (>48 hours) *modified Marshall scoring system 2 기부전유무와지속기간그리고국소또는전신합병증발생유무에따라구분한다. 장기부전과국소, 전신합병증이없는경우를경증, 48시간이내에회복되는장기부전이있거나국소또는전신합병증이있는경우를중등도중증, 48시간이상지속되는장기부전이있는경우에는중증급성췌장염으로구분한다 (Table 2). 2 2. 급성췌장염의초기치료급성췌장염치료에있어근간이되고가장중요한것은적절한수액공급이다. 급성췌장염발생첫 24시간동안의적절한수액공급은사망률과합병증감소에밀접한관련이있다. 4 일반적으로급성췌장염에서발생하는체액량감소는체액이신장이나위장관을통해체외로배출되어발생하는것이아니고체액의재배치에의해발생하는것이다. 그러므로적정량을넘어선과도한수액공급은오히려좋지않은결과가초래될수있다. 과거에는급성췌장염초기 24시간동안평균 4.5L 정도로다량의수액을공급한경우에입원기간과사망률을낮춘다고하여다량의수액공급이일반적으로시행되었다. 5 그러나최근연구에의하면급성췌장염발병초기 24시간동안 4.1L 이상다량으로수액을공급한경우호흡부전, 신부전등의장기부전발생이높았다. 6 또한과도한수액공급을실시하여헤마토크리트수치를빠르게감소시킨경우폐혈증발생이높았고입원기간중사망률도높았다. 7 그러므로현재급성췌장염초기 24시간동안수액은 2.5 4L 정도투여하거나소변이 0.5 ml/kg/hr 이상유지되게공급하는것이권유되고있다. 8 수액의종류는 Ringer s lactate 이용한경우에생리식염수를투여한경우와비교하여 24시간후 C-반응단백감소가유의하게높았고전신염증성반응증후군 (systemic inflammatory response syndrome) 의빈도도낮았다. 9 이러한결과는생리식염수투여는고염소대사성산증 (hyperchloremic metabolic acidosis) 을유발할수있고대사성산증은췌장염을유발하고악화시키며중증급성췌장 염의진행과연관이있다. 10,11 Ringer s lactate 는생리식염수에비해산염기균형이좋은수액 (ph-balanced solution) 이므로대사성산증이발생할위험이적기때문에초기수액으로생리식염수보다효과적이다. 급성췌장염발병초기수액공급에대해정리하면수액종류는생리식염수보다는 Ringer s lactate를 5 10 ml/kg/h 속도로주입하여맥박수가분당 120 회미만, 평균동맥압은 65 85 mmhg, 소변량이 0.5 1 ml/kg/h 이상또는헤마토크리트가 35 44% 중 4가지중 1가지이상만족할수있도록투여한다. 이후순환혈액량을재확인하여적절한수액의투여량과속도를재조절한다. 8 금식은현재도중요하게여겨지고있는급성췌장염의치료원칙중하나로 췌장휴식 을실시하자는것이이론적배경이다. 금식이치료에중요하다고제시된근거로는십이지장내음식물은췌장효소분비를자극하고이에따라췌장내에서단백분해효소 (protease) 가활성화되어급성췌장염의발병기전인선방세포의 자가소화 (autodigestion) 가유발되어췌장염이악화되는악순환이발생한다는것이다. 그러나실제급성췌장염에서췌장효소분비는췌장의무반응으로인해감소된다. 또한장기간의금식은장점막의위축을유발하여장장벽 (gut barrier) 의기능을저하시켜대장으로부터세균전사 (bacterial translocation) 가유발되어감염의합병증을증가시킨다. 12,13 그러므로최근에는가능한조기에장관을통한영양공급이추천되고있다. 경구를통한영양공급은진통제를복용하지않고도복통, 압통등이없고구토와장마비가없는경우에는혈청아밀라제, 리파제수치와관계없이실시할수있다. 감염성췌장괴사가있는경우에사망률은매우높다. 괴사성급성췌장염에서 ciprofloxacin, metronidazole, meropenem과같은예방적항생제사용에대한대규모연구에서예방적으로항생제를사용한경우와사용하지않은경우를비교한결과장기부전, 감염성췌장괴사발생과사망률에있어두군간에차이가없어현재는감염이확인되지않은중증급성췌 - 121 -

- 2018 년대한내과학회춘계학술대회 - Table 3. Terms used in the new classification based on contrast-enhanced computed tomography Interstitial edematous pancreatitis: inflammation or stranding in the pancreatic and/or peripancreatic tissues without tissue necrosis pancreatic parenchyma enhances with the contrast agent lack of peripancreatic necrosis necrotizing pancreatitis: pancreatic parenchymal necrosis and/or peripancreatic necrosis pancreatic parenchymal areas without enhancement by intravenous contrast agent and/or peripancreatic necrosis (see below acute necrotic collection and walled off necrosis) acute peripancreatic fluid collection: peripancreatic fluid occurring in the setting of interstitial edematous pancreatitis; this peripancreatic fluid occurs within the first 4 weeks of interstitial edematous pancreatitis homogeneous fluid adjacent to pancreas confined by peripancreatic fascial planes no recognizable wall pancreatic pseudocyst: an encapsulated, well defined collection of fluid but no or minimal solid components which occurs >4 weeks after onset of interstitial edematous pancreatitis. well circumscribed, homogeneous, round or oval fluid collection no solid component well defined wall occurs only in interstitial edematous pancreatitis acute necrotic collection: a collection of both fluid and solid components (necrosis) occurring during necrotizing pancreatitis. This collection can involve the pancreatic and/or the peripancreatic tissues heterogeneous, varying of non liquid density no encapsulating wall intrapancreatic and/or extrapancreatic walled off necrosis: a mature, encapsulated acute necrotic collection with a well defined inflammatory wall; these tend to mature >4 weeks after onset of necrotizing pancreatitis heterogenous liquid and non liquid density well defined wall intrapancreatic and/or extrapancreatic 장염에서예방적항생제사용은권유되고있지않다. 대장으로부터세균전사를줄이기위해실시하는선택적대장정결의효과에대해서는추가연구가필요하며프로바이오틱스 (probiotics) 사용역시권유되고있지않다. 8,14-16 3. 급성췌장염의국소합병증과치료급성췌장염초기체액이혈관외부로유출되어췌장내부또는위부에액체가고이는경우를액체고임 (pancreatic and/or peripancreatic fluid collection, PFC) 이라고정의한다. PFC는괴사조직포함여부에따른액체의성상, 발생시기와지속기간에따라급성췌장주위액체고임 (acute peripancreatic fluid collection, APFC), 급성괴사고임 (acute necrotic collection, ANC), 가성낭종 (pancreatic pseudocyst, PP), 벽괴사 (walled-off necrosis, WON) 로구분한다 (Table 3). 2 APFC 는급성간질성췌장염의초기에발생하며액체고임이벽에싸여있지않고후복강내정상근막면과의구분이가능하고액체의성상이균질하고무균성이다. APFC 는특별한증상이없는경우가대부분으로치료를위해중재적시술은필요하지않다. PP는급성간질성췌장염발생후최소 4주이상경과하여췌관으로부터유출된췌장효소를포함한고형괴사조직이없는췌장액또는췌장주위액체고임이얇은섬유성막으로싸인경우로정의되며급성췌장염의약 6 20% 정도에서발생하고췌관손상에의해내용물이췌장효소로만구성되어있는경우를진성가성낭종 (true pseudocyst) 이라한다. 2,17 과거 PP의치료는 6 cm 이상크기이거나크기가증가하는경우중재적시술의적응증이되었다. 18 그러나현재는증상이없는 PP의경우에는크기에상관없이중재적시술은필요하지않고 3 6개월간격으로초음파검사를통 - 122 -

- 도재혁. 급성및만성췌장염합병증. 어떻게치료하고추적관찰하여야하는가? - 해추적관찰을실시한다. 그러나복통, 감염, 출혈등의증상이나합병증이발생한 PP는영상의학적중재술, 내시경시술또는수술적배액이필요하다. 19,20 급성괴사성췌장염발생첫 4주기간동안췌장내부또는췌장외부에괴사된조직이고여있는경우를 ANC로정의한다. WON 은 ANC가발생최소 4주이상경과후 ANC 외부에염증성벽이형성된것으로괴사조직에의한액체와고형물질들로구성되어있다. 2 감염이없는 ANC는특별한치료가필요하지않다. 그러나발열, 복통의악화, 백혈구증가, 조영증강복부CT에서괴사부위에가스가관찰되거나가스 / 액체층 (gas/fluid level) 이보이는등감염이의심되는경우에는먼저광범위항생제를사용하여감염을완화시키고최소 4주정도경과하여벽이형성되는 WON이되어괴사조직과정상조직의구분이가능하고괴사조직이부드럽게액화된후중재적시술을실시하는것이합병증의위험을줄일수있다. 그러나환자상태가항생제투여만으로는효과가없을것으로판단되면경피적배액술을실시한후 4주정도경과하여벽이형성된후중재적시술을실시한다. 즉, 감염성괴사가발생한경우에는항생제만투여하거나또는항생제투여와함께경피적배액술을실시한후수주일정도시간경과후벽이형성되면경피적괴사제거술또는내시경적괴사제거술을실시하고경우에따라복강경을통한최소한의침습적괴사조직제거술을실시한다. 즉, 치료는최소침습적 (minimal invasive) 방법을통한시술을먼저실시하고단계적으로침습적시술로올리는접근방법 (step-up) 이합병증과사망률을감소시킨다. 21,22 최근많이사용되고있는내시경적배액술은경피적배액술과비교하여경피누공형성, 감염의위험성이적고입원기간을단축할수있는장점이있다. 23 만성췌장염 1. 정의와발생기전만성췌장염은유전, 환경적요인등여러위험인자들에의해유발되는지속적인병리학적반응으로인해췌장실질손상이발생하는병리학적섬유-염증증후군으로조직학적, 기능적으로췌장에비가역적인변화가발생한상태이다. 24 만성췌장염의발생기전에대해서는몇가지가설들이제기되어있다. 산화손상가설 (oxidative stress theory) 은간세포내에서독성물질해독과정중에발생한자유기 (free radical) 와같는산화부산물과 malondialdehyde, glutathione 같은지질 과산화 (lipid peroxidation) 부산물들이담즙을통해담관으로배출되어췌관으로역류하여췌관과선방세포에산화손상이발생하여섬유화가초래된다는가설이다. 독성-대사가설 (Toxic-Metabolic theory) 는알코올이세포내대사과정의변화를초래하여직접선방세포에손상을준다는것으로알코올이선방세포세포질내지질 (lipid) 의축적을유발하여지방변성을초래하여세포괴사를통해섬유화를초래한다는가설이다. 췌석-췌관폐쇄가설 (stone and ductal obstruction theory) 은알코올이췌장의외분비기능을변화시켜췌장액의결석형성능을증가시켜췌관내에췌석이형성된후이췌석의자극에의해췌관폐쇄와함께췌관상피세포에궤양과반흔발생하여췌장위축과섬유화가발생한다는가설이다. 괴사-섬유화가설 (necrosis-fibrosis theory) 은반복적인급성췌장염에의한염증과괴사에의해췌장세관주위 (peri-ductular area) 에반흔이형성되고이로인해췌장액의정체가발생하여췌석이형성되어췌관폐쇄가일어나췌장위축과섬유화가발생한다는것이다. 원발성췌관가설 (primary duct theory) 은비알코올성만성췌장염에서췌관상피세포에가해진면역학적인자극에의해췌관상피세포에염증과반흔이발생한다는것으로만성췌장염도원발경화성담관염 (primary sclerosing cholangitis) 과같이자가면역질환이라는가설이다. 25 최근에제기된 sentinel acute pancreatitis event (SAPE) 가설은현재까지밝혀진분자생물학적세포학적지식을기반으로산화스트레스가설, 독성- 대사가설, 괴사- 섬유화가설을합친것이다. SAPE 가설은여러자극에의해선방세포내에서트립신이활성화되어최초의급성췌장염 (sentinel event) 이발생한다. 최초의급성췌장염즉, sentinel event는췌장염에따른초기와후기염증성반응모두에관여한다. 초기염증성반응은중성구, 림프구와같은염증성세포들에의해이루어지며초기염증성반응동안분비된여러사이토카인들은항염증세포의침윤을유도한다. 급성췌장염의후기염증성반응은성상세포 (stellate cells) 를포함한섬유화유도세포들로구성되어췌장의섬유화가발생할수있는상태의단계에놓이게된다. 이단계에서알코올이나산화스트레스같은급성췌장염을유발요인들의자극이더이상없으면췌장은정상으로회복되나급성췌장염을유발할수있는자극들이다시가해지면지속적으로사이토카인이분비되고성상세포의활성화가지속되어췌장의섬유화가진행된다는가설이다. 26 급성췌장염에서만성췌장염으로진행하는빈도는처음급성췌장염이발생한환자에서는 10%, 그리고재발성급성췌장염환 - 123 -

- 2018 년대한내과학회춘계학술대회 - 자에서는 36% 정도이다. 만성췌장염발생의위험인자는흡연, 음주였고남자가여자보다만성췌장염으로이행되는경우가많다. 27 2. 만성췌장염의합병증과치료 1) 복통복통은만성췌장염의중요한합병증이다. 췌장의통각수용신호는세포의후근신경절에있는일차통각구심경로를통해전파되어척수의후각을통해중추신경계로전해진다. 만성췌장염에서복통발생기전은염증과섬유화로인해췌장신경의비후가일어나통각구심신경에대한반응이증가하고말초신경계과중추신경계의과민반응으로인한통각과민 (hyperalgesia) 이발생하거나정상적인자극에대해서도통증을느끼는무해자극통증 (allodynia) 발생하기때문이다. 28 복통완화를위해사용하는진통제는세계보건기구에서제안한 3단계사다리 (three-step ladder) 의원칙이표준진료지침으로이용된다. 이지침은통증이완화될때까지단계적으로진통제의종류와용량을증량하여통증을조절하는것을원칙으로한다. 그러나복통이매우심한경우에는처음부터마약성진통제를포함한강력한진통제를이용하여통증을조절한이후약의강도를낮추는방법도고려되어야한다. 29,30 진통제사용의첫단계는비스테로이드성항염증제 (Nonsteroidal anti-inflammatory drugs, NSAIDs) 를사용하여효과여부를확인한다. NSAIDs는근골격계통증조절에는 효과적이나위장관과심혈관계부작용으로내장통증조절효과는크지않다. 코데인 (codeine) 은약한마약성진통제로다른마약성진통제와같이오심, 변비, 소화불량등의부작용이발생할수있다. 트라마돌 (tramadol) 은약한아편유사작용과함께척수에서 serotonin 섭취효과가있어코데인보다통증조절에효과적이며중추신경계에작용하는강력한마약성진통제인모르핀 (morphine) 과비교해서위장관부작용은작다. 사람의위장관에는 μ-, δ- 그리고 κ-수용체등 3가지종류의마약수용체 (opioid receptor) 가존재하며마약성진통제의효과는이수용체들을통해이루어진다. 대부분의마약성진통제는 μ-수용체의활성화를통해작용하는데위장관에서기인하는통증의조절은 κ-수용체를활성화시키는것이더효과적이다. 31,32 옥시코돈 (oxycodone) 은 μ-, δ- 그리고 κ-수용체모두에작용함으로만성췌장염에서모르핀보다내장통증을완화시키는데효과적이다. 33 마약성진통제는경구또는첩포 (patch) 형태로사용할수있다. 경구와첩포두군간의진통효과는차이가없고첩포의경우 44% 에서피부부작용이발생하여첩포는만성췌장염의통증조절을위한 1차약제로는권유되고있지않다. 34 항불안제, 항우울제등도통증조절을위한보조제로사용할수있다. 최근에는 α-2-δ 리간드 (ligand) 인 pregabalin이만성췌장염통증조절에효과적이라고알려졌다. pregabalin의기전은칼슘채널인 α -2-δ에작용하여칼슘이시냅스전신경말단 (pre-synaptic nerve terminal) 으로유입되는것을차단하고 glutamate, noradrenalin, Fig 1. An illustration of the multidisciplinary approach recommended for managing pain in chronic pancreatitis. PPI: Proton pump inhibitor; TENS: Transcutaneous electrical nerve stimulation; SCS: Spinal cord stimulation; OIBD: Opioid-induced bowel dysfunction; TMS: Transcranial magnetic stimulation; ESWL: Extracorporeal shock wave lithotripsy. - 124 -

- 도재혁. 급성및만성췌장염합병증. 어떻게치료하고추적관찰하여야하는가? - substance P와같은흥분성신경전달물질의배출을줄여통증전달을줄인다. 35 cholecystokinin (CCK) 는췌관압력을올리고직접적으로중추신경계의통각경로를활성화시켜통증을유발한다. 췌장효소제는 CCK의분비를감소시켜통증을감소시킬수있을것으로기대하였으나메타연구에서췌장효소제는만성췌장염의통증조절에는효과가없었다. 36 만성췌장염에서는미량영양소의결핍으로인해산화손상이발생하고산화손상에의해생성된자유기에의해췌장에손상이발생하고염증이유도된다. 항산화제사용이통증을감소시키는도움이되는지에대해서는논란의여지가있으나일부환자에서만도움이된다. 또한금주, 금연그리고하루 20g 미만의저지방식이는통증의빈도를줄이는데도움이된다. 37 만성췌장염에서복통은췌장자체의원인으로발생하는경우가많으나가성낭종, 십이지장, 담도폐쇄, 소화성궤양, 비장정맥혈전등으로통증이발생하는경우도있기때문에통증의원인을파악하고치료하는것이중요하다 (Fig. 1). 38 2) 외분비기능부전 (exocrine dysfunction) 설사, 지방변, 체중감소등이주증상인외분비기능부전은췌장효소분비가정상의 10% 미만으로감소되면발생한다. 지방흡수장애가단백질흡수장애보다먼저발생하는데그이유는췌장기능저하에따라리파제분비가단백분해효소에비해더빨리감소하며단백분해효소는췌장이외에도위와소장에서도분비되며리파제에비해변성에강하기때문이다. 39,40 췌장효소분비는식사후공복에서보다 6 배까지빠르게상승하여식후 20분에서 60분내에최대치에도달한후감소하여 3 4 배수준으로 3 4 시간지속되다가공복수준으로회복된다. 정상성인에서리파제는식후평균 2,000 4,000 IU/min, 최대 3,000 6,000 IU/min 분비된다. 41 정상적으로식사후총 360,000 IU 이상의리파제가십이지장으로분비되며일반적으로총리파제의약 10% 정도만십이지장에있어도지방변을교정할수있다. 그러므로최소 30,000 IU 정도의리파제가식사와함께십이지장에도달되면지방변을예방할수있다. 39 그러나, 위산에의한분해와 Fig 2. Algorithm of the management of pancreatic enzyme non-responders. PERT, pancreatic enzyme replacement therapy; PPI, proton pump inhibitor; SIBD, small intestinal bacterial overgrowth syndrome. 리파제의불활성화에의해적절한양의리파제가십이지장으로도달하기위해서는정상식사에서는식사당 40,000 50,000 IU, 간식을섭취하는경우에는 10,000 25,000 IU의리파제가필요하다 (Table 4). 42,43 투여시기는췌장효소가위내부에서 1차적으로소화된음식물과함께십이지장으로배출되어야소화와흡수효과가증가함으로투여할전체용량의 1/2은식사를시작할때나머지 1/2은식사중간에투여한다. 44 췌장효소제투여에따른효과판정은증상호전, 체중증가, 영양지표들의호전등을기준으로한다. 45 췌장효소제효과가충분하지않은경우에는정확하게복용하였는지, 투여하는효소제의용량이적절한지, 위와십이지장내산도가낮은지, 세균의과증식이있는지등을확인하고교정해 Table 4. Key points of pancreatic enzyme replacement Individual dosing (severity of disease, composition of food, body weight) 2,000(1,000 4,000 U/g) lipase unit digest 1 g of fat Adult at least 40,000 (20,000 75,000) U of lipase per main meal, 10,000 25,000 U/snack Administration - with every meal or snack - in individual portions during the meal, or short time after starting the meal - 125 -

- 2018 년대한내과학회춘계학술대회 - Table 5. Currently available pancreatic enzyme products in Korea Brand name Preparation Ingredients Bearse Tablet, enteric-coated granule Lipase 15 mg Pancreatin 78.6 mg Beszyme Tablet Pancreatin 400 mg Bromelain 30 mg Creon Delayed-release capsule Enteric-coated microsphere Pancrelipase Creon 24000 Creon 40000 Enzyme activity (USP unit) Lipase Protease Amylase 24,000 4,200 36,000 10,000 33,000 31,000 24,000 40,000 76,000 100,000 120,000 103,600 Dages Capsule, enteric-coated Pancreatin 50 mg 14,500 4,000 6,500 Pancrelipase 13 mg Festal plus Tablet Pancreatin 315 mg 9,660 25,000 31,000 Gesterin Dragee Pancreatin 200 mg Bromelain 7,500 U 6,133 23,000 20,000 Norzyme Enteric-coated microsphere Norzyme 10000 Norzyme 25000 Norzyme 40000 10,000 25,000 40,000 28,125 78,125 93,750 31,125 93,375 103,750 Pancron Enteric-coated tablet Pancreatin 175 mg 5,366 22,000 31,000 주어야한다 (Fig. 2). 46 현재국내에서시판되고있는췌장효소제 (Table 5) 를정리하면판크레아틴 (pancreatin) 은돼지나소의췌장에서분리된비장제피형 (non-enteric coated) 제제로가격이저렴한장점이있으나위산에의해쉽게파괴되어위산분비억제제와같이투여하여야하고필요량보다많은양을복용하여야하는단점이있다. 장제피형 (enteric coated) 제제는위산에의한불활성화를방지할수있으나효소방출이일정하지않고십이지장에서분비되지않는경우가있다. 장제피형마이크로스피어 (enteric coated microsphere) 제제는위산에대한저항성이크고산도가 ph 5.0 5.5에서효소가방출되는특성이있어위산분비억제제가항상필요하지는않으며크기가작아음식물과같이이동하면서십이지장에서적절하게작용할수있는장점이있다. 47 3) 내분비기능부전 (Endocrine dysfunction) 만성췌장염에의한당뇨병은췌장암, 췌장수술또는외상, 혈색소증, 낭성섬유증과같이췌장의외분비기능부전에의해발생함으로미국당뇨병학회의분류기준에서 III. Other specific types 의 C. 항목 Disease of exocrine pancreas에해당되어 type 3c DM (T3cDM) 라고한다. 48 만성췌장염환자에서는매년공복혈당과당화혈색소를측정하여당뇨병발생여부를확인해야한다. T3cDM 는다른형태의당뇨병와비교하여저혈당과췌장암발생빈도가높은특징이있다. 49 치료는당화혈색소가 8% 미만인경한당뇨병인경우에는 metformin 단독치료를실시하는데 metformin은인슐린주사와비교하여저혈당발생이적고이론적으로는췌장암예방에도움이될수있다. 인슐린주사는인슐린감수성이높은만성췌장염환자에서사용하면저혈당위험이증가함으로주의하여사용하여야한다. 최근개발된 GLP-1 유사체와경구 DPP-4 억제제와같은인크레틴 (incretin) 기반항당뇨병제제는급성췌장염과췌장암발생의위험이증가할수있으므로가급적사용을피해야한다. 50,51 결론급성췌장염은대부분경증으로보존적치료로특별한합병증없이완치되나장기부전또는합병증이동반된중등도중증이상의급성췌장염은사망률이높아적극적인초기치료가예후와합병증발생에중요한영향을미친다. 급성췌장염에의해발생한급성췌장주위액체고임, 급성괴사고임, 가성낭종, 벽괴사등의국소합병증들은감염과증상이없는경우에는배액등침습적시술은필요하지않고주기적으로추적관찰을실시한다. 급성췌장염초기에급성췌장주위액체고임, 급성괴사고임등의국소합병증이있으면서감염이있으나환자의전신상태가안정되있는경우에는즉각적으로침습적시술을실시하기보다는항생제등을투여하고보 - 126 -

- 도재혁. 급성및만성췌장염합병증. 어떻게치료하고추적관찰하여야하는가? - 존적인치료를실시하면서급성췌장주위액체고임이나급성괴사고임주위에벽이형성되는 4주이후에영상의학적또는내시경적으로침습적시술을실시한다. 만성췌장염에의한복통, 외분비, 내분비기능부전등의합병증이발생한경우에는환자상태에따른맞춤치료를실시하며당뇨병과췌장암발생에대해주기적으로추적관찰을실시하여야한다. 참고문헌 1. Fagenholz PJ, Castillo CF, Harris NS, et al. Increasing United States hospital admissions for acute pancreatitis. 1988-2003. Ann Epidemiol 2007;17:491-497. 2. Banks PA, Bollen TL, Dervenis C, et al. Acute pancreatitis classification working group. Classification of acute pancreatitis-2012: revision of the Atlanta classification and definitions by international consensus. Gut 2012;62:102-111. 3. Yadav D, Lowenfels AB. Trends in the epidemiology of the first attack of acute pancreatitis: A systematic review. Pancreas 2006;33:323-330. 4. Tenner S, Baillie J, DeWitt J, Vege SS. American college of gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400-1415. 5. Warndorf MG, Kurtzman JT, Bartel MJ, et al. Early fluid resuscitation reduces morbidity among patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011;9:705-709. 6. de-madaria E, Soler-Sala G, Sanchez-Paya J, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol 2011;106: 1843-1850. 7. 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;123:1639-1644. 8. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence based guidelines for the management of acute pancreatitis. Pancreatology 2013;13(Suppl. 2):e1-15. 9. Wu BU, Hwang JQ, Gardner TH, et al. Lactated Ringer s solution reduces systemic inflammation compared with saline in patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011;9:710-717. 10. Wilkes NJ, Woolf R, Mutch M, et al. The effects of balanced versus saline-based hetastarch and crystalloid solutions on acid-base and electrolyte status and gastric mucosal perfusion in elderly surgical patients. Anesth Analg 2001;93: 811-816. 11. Noble MD, Romac J, Vigna SR, et al. A ph-sensitive, neurogenic pathway mediates disease severity in a model of post-ercp pancreatitis. Gut 2008;57:1566-1571. 12. Meier R, Ockenga J, Pertkiewicz M, et al. ESPEN Guidelines on enteral nutrition: pancreas. Clin Nutr 2006; 25: 275-284. 13. Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev 2010;1:CD0028372. 14. Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann Surg 2007;245:674-683. 15. Isenmann R, Runzi M, Kron M, et al. Prophylactic antibiotic treatment in patients with predicted severe acute pancreatitis: a placebo-controlled, double-blind trial. Gastroenterology 2004;126:997-1004. 16. Gou S, Yang Z, Liu T, Wu H, Wang C. Use of probiotics in the treatment of severe acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials. Crit Care 2014;18:R57. 17. Braha J, Tenner S. Fluid Collections and Pseudocysts as a Complication of Acute Pancreatitis. Gastrointest Endosc Clin N Am 2018;28:123-130. 18. Maringhini A, Uomo G, Patti R, et al. Pseudocysts in acute nonalcoholic pancreatitis: incidence and natural history. Dig Dis Sci 1999;44:1669-1673. 19. Vitas GJ, Sarr MG. Selected management of pancreatic pseudocysts: operative versus expectant management. Surgery 1992;111:123-130. 20. Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol 2013;108:1400-1415. 21. van Santvoort HC, Bakker OJ, Bollen TL, et al. A conservative and minimally invasive approach to necrotizing pancreatitis improves outcome. Gastroenterology 2011;141: 1254-263. 22. Forsmark CE, Vege SS, Wilcox CM. Acute Pancreatitis. N Engl J Med 2016;375:1972-1981. 23. Ge PS, Weizmann M, Watson RR. Pancreatic pseudocysts: advances in endoscopic management. Gastroenterol Clin N Am. 2016;45:9-27. 24. Kleeff J, Whitcomb DC, Shimosegawa T, et al. Chronic pancreatitis. Nat Rev Dis Primers. 2017;3:17060. 25. Stevens T, Conwel DL, Zuccaro G. Pathogenesis of Chronic Pancreatitis: An Evidence-Based Review of Past Theories and Recent Developments. Am J Gastroenterol 2004;99: 2256-2270. 26. Whitcomb DC. Hereditary pancreatitis: new insights into acute and chronic pancreatitis. Gut 1999;45:317-322. 27. Sankaran SJ, Xiao AY, Wu LM, Windsor JA, Forsmark CE, Petrov MS. Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis. Gastroenterology - 127 -

- 2018 년대한내과학회춘계학술대회 - 2015;149:1490-1500. 28. Singh VK, Drewes AM. Medical Management of Pain in Chronic Pancreatitis. Dig Dis Sci 2017;62:1721-1728. 29. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA 1995;274:1870-1873. 30. World Health Organization. Cancer Pain Relief. Geneva: World Health Organization;1986. 31. De Schepper HU, Cremonini F, Park MI, Camilleri M. Opioids and the gut: pharmacology and current clinical experience. Neurogastroenterol Motil 2004;16:383-394. 32. Sengupta JN, Su X, Gebhart GF. Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon. Gastroenterology 1996;111:968-980. 33. Staahl C, Dimcevski G, Andersen SD, et al. Differential effect of opioids in patients with chronic pancreatitis: an experimental pain study. Scand J Gastroenterol 2007;42:383-390. 34. Niemann T, Madsen LG, Larsen S, Thorsgaard N. Opioid treatment of painful chronic pancreatitis. Int J Pancreatol 2000;27:235-240. 35. Bouwense SA, Olesen SS, Drewes AM, Poley JW, van Goor H, Wilder-Smith OH. Effects of pregabalin on central sensitization in patients with chronic pancreatitis in a randomized, controlled trial. PLoS One 2012;7:e42096. 36. Brown A, Hughes M, Tenner S, Banks PA. Does pancreatic enzyme supplementation reduce pain in patients with chronic pancreatitis: a meta-analysis. Am J Gastroenterol 1997; 92:2032-2035. 37. Rustagi T, Njei B. Antioxidant therapy for pain reduction in patients with chronic pancreatitis: a systematic review and meta-analysis. Pancreas 2015;44:812-818. 38. Olesen SS, Juel J, Graversen C, Kolesnikov Y, Wilder- Smith O, Drewes AM. Pharmacological pain management in chronic pancreatitis. World J Gastroenterol 2013;19: 7292-7301. 39. Lankisch PG, Lembcke B, Wemken G, Creutzfeldt W. Functional reserve capacity of the exocrine pancreas. Digestion 1986;35:175-181. 40. Layer PH, DiMagno EP. Natural histories of alcoholic and idiopathic chronic pancreatitis. Pancreas 1996;12:318-320. 41. Keller J, Layer P. Human pancreatic exocrine response to nutrients in health and disease. Gut 2005;54(Suppl. 6):1-28. 42. Domínguez-Muñoz JE. Chronic pancreatitis and persistent steatorrhea: what is the correct dose of enzymes? Clin Gastroenterol Hepatol 2011;9:541-546. 43. Hammer HF. Pancreatic exocrine insufficiency: Diagnostic evaluation and replacement therapy with pancreatic enzymes. Dig Dis 2010;28:339-343. 44. Domínguez-Muñoz JE, Iglesias-García J, Iglesias-Rey M, Figueiras A, Vilariño-Insua M. Effect of the administration schedule on the therapeutic efficacy of oral pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency: a randomized, three-way crossover study. Aliment Pharmacol Ther 2005;21:993-1000. 45. Toouli J, Biankin AV, Oliver MR, Pearce CB, Wilson JS, Wray NH. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations. Med J Aust 2010;193:461-467. 46. Pongprasobchai S. Maldigestion from pancreatic exocrine insufficiency. Journal of Gastroenterology and Hepatology 2013;28(Suppl. 4):99-102. 47. Lebenthal E, Rolston DD, Holsclaw DS, Jr. Enzyme therapy for pancreatic insufficiency: present status and future needs. Pancreas 1994;9:1-12. 48. American Diabetes Association: Diagnosis and classification of diabetes. Diab Care 2011;34(Suppl. 1):S62-S69. 49. Cui Y, Andersen DK. Diabetes and pancreatic cancer. Endocr Relat Cancer. 2012;19:F9-F26. 50. Hart PA, Bellin MD, Andersen DK, et al. Type 3c (pancreatogenic) diabetes mellitus secondary to chronic pancreatitis and pancreatic cancer. Lancet Gastroenterol Hepatol 2016;1:226-237. 51. Elashoff M, Matveyenko AV, Gier B, Elashoff ZR, Butler PC. Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology. 2011; 141:150-56. - 128 -