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1 Korean J Gastroenterol Vol. 66 No. 3, pissn eissn REVIEW ARTICLE 급성췌장염치료의최신지견 이준규 동국대학교의과대학내과학교실, 동국대학교일산병원내과 Recent Advances in Management of Acute Pancreatitis Jun Kyu Lee Department of Internal Medicine, Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang, Korea Acute pancreatitis is common but remains a condition with significant morbidity and mortality. Despite a better understanding of the pathophysiology of acute pancreatitis achieved during the past few decades, there is no specific pharmacologic entity available. Therefore, supportive care is still the mainstay of treatment. Recently, novel interventions for increasing survival and minimizing morbidity have been investigated, which are highlighted in this review. (Korean J Gastroenterol 2015;66: ) Key Words: Acute pancreatitis; Fluid therapy; Nutrition; Infected necrosis; Cholangiopancreatography, endoscopic retrograde 서론 급성췌장염 (acute pancreatitis) 은선방세포 (acinar cell) 내에서비정상적으로조기에활성화된소화효소에의하여췌장이자가소화 (autodigestion) 되어발생하는염증성질환이다. 대부분의환자는췌장손상이경미하여보존적치료만으로도합병증없이완전히회복되지만, 약 15-20% 에서는여러가지국소적및전신적합병증이동반되며, 이중 15-30% 는사망에이르게되므로보다적극적인치료가요구된다. 본고에서는급성췌장염의치료에있어서최근이루어진발전과아직해결되지않고있는쟁점에대하여살펴보기로한다. 본론 1. 통증조절급성췌장염환자의주증상이복통이고, 심한통증은복벽의운동을제한하여호흡기능을저하시킬수있으므로통증은적극적으로조절하여야한다. 하지만실제로는많은연구 가이루어지지않아, 2013년시도되었던체계적문헌고찰 (systematic review) 에서는진통제간의효과를비교하였던무작위대조연구의질이낮아결론을도출할수없다고하였다. 1 이론적으로는모르핀 (morphine) 을투여할경우오디괄약근 (sphincter of Oddi) 의압력을높여증상을악화시킬수있지만, 그근거는희박하다. 2 현상황에서는수술전후급성통증관리지침을따르는것이합리적일것으로보인다 초기수액요법급성췌장염의초기에수액공급이불충분할경우에는괴사의발생이나사망률이증가하므로, 4-7 혈액내유효혈액량을유지하기위한적극적인수액공급은급성췌장염의초기치료에있어서매우중요하게인식되어왔다. 8 하지만최근들어수액공급이과도한경우에는오히려폐부종과같은합병증이발생할수있다는결과들이잇달아발표되어, 9-11 환자별최적화전략의필요성이강조되고있다. 12 이와관련하여 Wu 등 13 은초기에 20 ml/kg의수액을일시에투여한후 3 ml/kg/hr를유지용량으로투여하면서임상상태를확인하고 CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright Korean Society of Gastroenterology. 교신저자 : 이준규, 10326, 고양시일산동구동국로 27, 동국대학교의과대학내과학교실, 동국대학교일산병원내과 Correspondence to: Jun Kyu Lee, Department of Internal Medicine, Dongguk University College of Medicine, Dongguk University Ilsan Hospital, Goyang 10326, Korea. Tel: , Fax: , jeromee1971@yahoo.co.kr Financial support: None. Conflict of interest: None. Korean J Gastroenterol, Vol. 66 No. 3, September

2 136 이준규. 급성췌장염치료의최신지견 혈중요소농도 (BUN) 를추적하여감소하지않는경우에는일시투여량을반복투여, 감소하는경우에는유지용량을 1.5 ml/kg/hr로감소시키는목적지향수액요법 (goal-directed fluid resuscitation) 이안전하고타당하다고주장하였다. 이러한접근은 BUN이중증의질환을예측할수있는신뢰성높으며경제적인인자로서, 입원시 BUN이 20 mg ( 또는 7.14 mmol/l) 이상인경우에사망률의교차비 (OR) 가 4.6, 절대치와관계없이입원 24시간이내에 BUN이상승한경우에는사망률의교차비가 4.3에이르렀다는국제적타당성연구의결과에근거한다 년발표된 International Association of Pancreatology/American Pancreatic Association (IAP/APA) 가이드라인에서는심박수 ( 분당 120회이하 ), 소변량 ( ml/kg/hr 이상 ), 헤마토크리트 (35-44%) 등이목표에도달할때까지 5-10 ml/kg/hr의속도로수액을투여하도록권고하였는데, 대개의환자에서첫 24시간이내에 2,500-4,000 ml면충분하다고언급하였다. 15 투여수액의종류에대해서는연구가비교적많이이루어지지않았다. 앞서언급한 Wu 등 13 의연구에서 lactated Ringer s solution이투여된경우에생리식염수에비해전신염증반응증후군 (systemic inflammatory response syndrome, SIRS) 의발생이 80% 이상적었던것으로나타났는데, 이는산-염기불균형의교정등의부가적효과에기인한것으로여겨진다. 16 또다른연구에서는생리식염수, hydroxyethyl starch (HES), 글루타민 (glutamine) 의병합투여가염증반응을완화하는것으로나타났다 년발표된 American College of Gastroenterology (ACG) 가이드라인에서는 lactated Ringer s solution이등장성정질용액 (isotonic crystalloid fluid) 보다선호될수있다고기술하였고, 18 IAP/ APA 가이드라인에서는 lactated Ringer s solution은고칼슘혈증이동반된환자에서는투여되어서는안된다고언급되어있다. 최근중국에서시행된비교적대규모의무작위연구에서는 200명의환자를 3군으로나누어중증의급성췌장염환자에있어서신선동결혈장투여의효과를연구하였다. 19 모든환자는증상발현 24시간이내에중환자실에입원하였으며, 생리식염수와 HES를투여받았는데, 한치료군에서는하루 2단위의신선동결혈장이 3일간추가로투여되었다. 투여속도는대조군에있어서는첫 24시간동안의생체징후, 요량, 헤마토크리트에의해결정되었고, 다른두군에서는이외에도중심정맥압이나동맥압측정등의침습적감시가시행되었다. 침습적감시를시행한두군에서는대조군에비하여인공호흡기사용이나중환자실재원일수및복부구획증후군 (abdominal compartment syndrome), 장기부전, 사망률등의감소효과가나타났으며, 특히신선동결혈장투여군에서가장좋은성적이보고되었다. 3. 영양공급전통적으로췌장의안정을위한금식은급성췌장염에있어서필수적치료라고여겨져왔지만그근거는희박하다. 오히려금식은장점막을위축시키고이로인하여장내세균의췌장전위 (translocation) 을조장하여감염성합병증을유발할수있다. 20 또한함께시행되는총정맥영양법 (total parenteral nutrition, TPN) 은그자체가염증반응을악화시킬가능성이있으며, 21 추가적비용및카테터감염증등도문제가될수있다. 2010년발표된중증의급성췌장염환자에서시행된 8개의무작위대조연구를대상으로한 Cochrane 메타분석 (Cochrane meta-analysis) 에서경장영양법 (enteral nutrition, EN) 은 TPN에비하여사망률, 다장기부전, 감염성합병증, 수술의필요성을낮추고, 재원일수를감소시키는것으로나타났다. 22 또한 Sun 등 23 은입원후 48시간이내 EN을시작한경우에후속되는면역억제없이과도한면역반응을조절할수있다고하였다. 하지만최근네덜란드에서진행되었던 PYTHON (Pancreatitis, very early compared with selective delayed start Of enteral feeding) trial에서는합병증의발생이예상되는급성췌장염환자에있어서입원 24 시간이내에시작되었던조기비장관 (nasoenteric) 영양법이 72시간이후환자의요청으로진행되었던경구영양에비하여감염이나사망률을줄이지못하는것으로나타났다. 24 한편경구섭취가불가능한환자에있어서전통적으로비공장관 (nasojejunal tube) 이비위관 (nasogastric tube) 보다우선시되어왔지만두군을비교한무작위대조연구에서차이가발견되지않아, 현재는더간편한비위관삽입이추천되고있다 개의무작위연구를대상으로한메타분석에서 EN 의성분은급성췌장염의예후에영향을미치지않는것으로나타났다. 28 완전한영양공급이되지않더라도경구섭취를지속하여소화관통합성 (integrity) 을유지하는것이중요하다. 중증의경우보다임상적중요성이떨어지므로많은연구가이루어지지않은경증의경우에도조기에 EN을시작한경우에회복이빠른것으로보고되었으며, 29,30 저지방고형식 (low fat solid diet) 이맑은유동식 (clear liquid diet) 에비하여더나은임상경과를보이는것으로나타났다. 31,32 또다른연구에서담석이있는경우, 금식시간이긴경우, 정상식사로빨리진행한경우에복통의재발이흔한것으로보고되었다 감염성합병증의예방급성췌장염에있어서감염성합병증의발생은사망률에큰영향을미치며, 균혈증 (bacteremia) 은사망률의독립적위험인자로서감염성괴사의위험성을증가시킨다. 34 따라서예방적항생제투여에대한많은무작위연구들이시행되었지 The Korean Journal of Gastroenterology

3 Lee JK. Recent Advances in Management of Acute Pancreatitis 137 만, 선정기준, 투여항생제의종류등이상이하여그효과에대해서는아직까지일관된결론에이르지못하고있다. 비교적최근발표된 2편의메타분석은예방적항생제의사용을추천하지않고있다. 35,36 7개의무작위대조연구의 404명을대상으로한 Cochrane 메타분석에서 imipenem의췌장감염예방을제외한다른효과는관찰되지않았다 개연구의 841명을대상으로한또다른메타분석에서도사망률이나감염성합병증의예방효과는관찰되지않았다. 36 예방적항생제를투여할경우진균 37,38 이나 Clostridium difficile 39 감염의위험성이증가할가능성도제기되고있다. 급성췌장염이아닌일반적인중환자실환자에있어서선택적소화관살균 (selective decontamination of digestive tract) 은사망률을감소시키는것으로알려져있다. 40 Luiten 등 41 은급성췌장염에도이러한원리를적용하여중증의환자에서 norfloxacin, colistin, amphotericin 등을투여하여선택적소화관살균을시행한경우에감염성합병증과사망률을줄일수있었다고보고하였다. 하지만선택적살균과함께소화관통합성을유지하기위하여 EN을함께시행한 Sawa 등 42 의연구에서는효과가확인되지않았다. 선택적소화관살균법은항생제에대한내성의발생을조장할수있고, 그람양성균이나진균에의한감염의위험성을증가시킬수있으므로주의하여야한다. 4개의무작위대조연구의 428명의환자를대상으로한메타분석에서프로바이오틱스예방 (probiotics prophylaxis) 은감염성합병증과사망률을감소시키지못하는것으로나타났다. 43 특히중증이예측되는환자를대상으로네덜란드에서대규모로진행되었던 PROPATRIA (PRObiotic ProphylAxis in patients with predicted severe Acute pancreatitis) trial에서는오히려장관허혈및사망률을증가시키는것으로보고되어, 급성췌장염환자에서프로바이오틱스는추천되지않는다. 44 한편췌장이외기관의감염성합병증도급성췌장염환자의예후에영향을미칠수있다. 네덜란드에서 731명의처음진단된급성췌장염환자를대상으로시행된연구에서약 25% 가입원기간중균혈증이나폐렴을경험하는것으로나타났는데, 감염성췌장괴사의경우특징적으로발병 4주이후에발생하는반면이러한감염증은대부분 2주이내에나타났다. 34 미국에서시행되었던또다른연구에서는급성췌장염환자에서병원내감염이발생할경우질환의중증도를보정하더라도사망의위험성이 2배가량증가하는것으로조사되었다. 45 따라서일반적으로예방적항생제의투여는추천되지않더라도췌장이외의장기에서발생하는감염증에대하여철저히감시하고필요한경우에는적극적으로치료하여야한다. 5. 감염성췌장괴사의치료전통적으로감염성췌장괴사는일단진단되면응급수술을통해제거해야한다고여겨져왔다. 하지만많은수의환자가 SIRS나다장기부전에이환되어전신마취에적합하지않은상태이고, 실제로수술을시행하더라도감염된조직과그렇지않은조직을명확하게구별하여절제하는것이쉽지않으며, 감염되지않은조직에오히려감염이유발되는등의문제점이지속적으로제기되었다. 이에수술은가급적발병 4주이후로미루는대신내과적치료및중재적시술을적극적으로시행하는데관한많은연구가진행되었다 년발표된 8개연구 324명의환자를대상으로한메타분석에서 64% 의환자가보존적치료로회복되었는데, 사망률은 12% 로낮았으며, 수술적치료는 26% 에서만필요하였던것으로나타났다. 50 최근네덜란드에서다기관으로시행되었던 PANTER (PAncreatitis, Necrosectomy versus a minimally invasive step up approach) trial에서는감염성췌장괴사의치료에있어단계적접근 (step-up approach) 과개복괴사조직절제술을무작위적으로비교하였다. 51 단계적접근군에있어서는항생제투여와함께경피적배액관을삽입하여관류세척하며필요한경우에는구경을증가시켰는데, 72시간내에상태가호전되지않는경우에는후복막강으로접근하여최소침습조직제거술 (minimally invasive debridement) 이시행되었다. 단계적접근군에서 35% 는경피적배액술만으로치료되었으며, 수술군에비하여중증의합병증이나사망률이 29% 낮게나타났다. 감염성췌장괴사에서이러한단계적접근전략은여러치료지침에서도우선적으로추천되고있으며, 48,15 현재네덜란드에서내시경적단계적접근과수술적단계적접근을비교하는 TENSION (Transluminal ENdoscopic Step-up approach versus minimally Invasive surgical step-up approach in patients with Infected pancreatic Necrosis) trial도진행중이다 (ISRCTN ). 52 내시경적괴사조직절제술은일종의자연개구내시경수술 (natural orifice transluminal endoscopic surgery, NOTES) 로서, 최소침습적임과동시에전신마취없이시행할수있는장점이있다. 네덜란드에서시행되었던 PENGUIN (Pancreatitis ENdoscopic transgastric versus primary necrosectomy in patients with Infected pancreatic Necrosis) trial에서는감염성구역성괴사 (walled-off necrosis, WON) 환자에대한괴사조직제거술에있어서내시경과수술을비교하였다. 53 이연구에서내시경치료는 interleukin (IL)-6 등염증표지자의혈중농도, 다장기부전의발생, 복강내출혈, 누공의형성, 사망률등을 60% 가량감소시키는것으로나타났다. 이러한내시경적배액술은경피적배액술과비교하였을때에도췌장 Vol. 66 No. 3, September 2015

4 138 이준규. 급성췌장염치료의최신지견 루를형성할가능성이낮은장점이있으나, 일차적배액방법에대해서는더많은연구가필요한상황이다. 한편외과적영역에서도기존의개복수술을대신하여비디오후복막강괴사조직절제술 (video-assisted retroperitoneal debridement) 이나최소접근후복막강췌장괴사조직절제술 (minimal access retroperitoneal pancreatic necrosectomy) 과같은최소침습수술이발전하고있다 이러한여러가지치료방법은실제환자의치료에있어서는서로경쟁적이지않으며, 각기관의경험및숙련도에따라상호보완적으로적용되어야한다. 6. 복부구획증후군복부구획증후군은원인질환자체또는과도한수액투여에의한부종에의해복강내압력상승 (intra-abdominal hypertension) 이발생하고, 이에따라심장의전부하감소및후부하증가가유발되어심박출량이떨어지며, 주요장기로의혈액공급에장애가발생하는경우를말한다. 여러가지내외과적질환에의하여유발될수있는데, 일단발생하면중환자실입원환자의사망률이급격히높아지는것으로알려져있다. Chen 등 58 은 74명의중중의급성췌장염환자중 44명 (59.5%) 에서도뇨관으로측정한복강내압력이 12 mmhg 이상으로상승하였다고보고하였으며, De Waele와 Leppäniemi 59 도 44 명중 21명 (78%) 에서복강내압력이 15 mmhg 이상으로상승하였다고하였다. Bezmarevic 등 60 은복강내압력상승이혈청 procalcitonin 농도와상관관계가있으며, 중증도예측인자로사용될수있다고하였다. 일반적인경우에일단복강내압력상승또는복부구획증후군으로진단되면즉시비위관을삽입하고하제와근육이완제등을투여하여압력을낮추어야하며, 반응이없을경우수술까지고려하여야한다. 현재세르비아에서급성췌장염환자에서복부구획증후군이발생한경우에있어서개복감암술과배액관삽입을비교하는 DECOMPRESS (Decompressive laparotomy with temporary abdominal Closure versus percutaneous puncture with placement of abdominal catheter in Patients with abdominal compartment Syndrome during acute pancreatitis) trial이진행중이다 (NCT ) 급성담석성췌장염에서 ERCP의역할담석에의한담췌공통관 (biliopancreatic duct) 의폐쇄는췌장염을유발하며, 폐쇄기간이길어질경우질병의경과를악화시킬수있음은여러동물실험및임상연구에서잘알려져있다 따라서담석을제거하거나담관을감압할수있는내시경적역행성담췌관조영술 (ERCP) 은급성담석성췌장 염의치료에있어서매우중요한역할을차지한다. 하지만췌장염을유발하는담석은대개크기가작아저절로빠져나가기쉬운반면 ERCP는시술관련합병증의빈도가낮지않은침습적시술이므로실제시행여부는신중히결정되어야한다. 일단담관염이동반된경우가발병 24-72시간내에시행하는응급 ERCP의적응증에해당한다는데에서는이견이없는것으로보인다. 66,67 하지만급성담석성췌장염환자에서담관염동반여부의구체적진단기준에있어서는논의의여지가있다. 연구에따라서 Charcot 삼징후 68 나전문가의견 69 등이적용되었으며, 아예언급이없는경우도있다. 65,70 최근개정된 Tokyo 가이드라인 (TG-13) 에서는전신적염증반응이있고간기능이상이동반된경우를담관염의의심진단 (suspected diagnosis) 으로정의하고있는데, 67 이러한기준이적용된다면실제로불필요한 ERCP가너무많이시행될우려가있다. 현재네덜란드에서는중증이예측되지만담관염이동반되지않은환자들을대상으로하는다기관무작위연구 APEC (Acute biliary Pancreatitis: early Endoscopic retrograde cholangiography plus sphincterotomy versus Conservative treatment) trial이진행중이다 (ISRCTN ). 71 마찬가지로여러연구에서담관폐쇄가지속되는경우 (persistent biliary obstruction) 도응급 ERCP의적응증으로제시되고있는데, 이에대해서도재고가필요하다. 흔히생화학적검사에서담즙정체 (cholestasis) 가있거나영상의학적검사에서담석이보이는경우가그기준으로사용되고있지만급성담석성췌장염의초기에는이러한검사의정확도에있어서제한이있으므로주의해서해석하여야한다. 76,77 경증의급성담석성췌장염환자에서응급 ERCP가도움이되지않는다는것은여러지침에서공통적으로제시되고있지만, 72,73,75 중증의질환에있어서는의견의통일이이루어지지않고있다. 영국가이드라인에서는중증의급성담석성췌장염이예상되는경우에는응급 ERCP의시행을추천하고있지만, 75 미국소화기학회 (American Gastroenterological Association) 및이탈리아가이드라인에서는논란의여지가있다고하였으며, 73,74 IAP/APA 가이드라인에서는적응증에해당하지않는다고기술하고있다. 15 이는근거가되는연구들에있어서참여기준, 중증도예측시스템, ERCP 시행시점및시술자의숙련도등이상이한데기인한다고보인다. 가장최근의 Cochrane 메타분석에서는급성담석성췌장염환자에있어서예상되는중증도와관계없이일률적인조기 (early routine) ERCP가사망률이나국소및전신적합병증의감소에있어효과가없다고하였다 혈액여과및복막투석중증의급성췌장염에있어서는췌장및주위조직에서국 The Korean Journal of Gastroenterology

5 Lee JK. Recent Advances in Management of Acute Pancreatitis 139 소적으로유래한각종사이토카인 (cytokine) 등의염증매개물질이체순환으로흡수되어전신적인다장기부전을유발하므로혈액여과 (hemofiltration) 및복막투석등을통해이러한염증매개물질을효과적으로제거한다면염증의진행을차단할수있을것으로여겨진다. 중국을중심으로이러한연구가진행되었는데, 비록크지않은규모였지만혈액여과단독또는복막투석병합치료를통해혈중사이토카인농도, 장기부전및감염성괴사의발생, 사망률등을낮출수있는것으로보고되었다 하지만혈역학적으로불안정한환자에있어서혈액여과자체가효과적으로시행되지않았던비율이나시술관련합병증등에대한세부정보가부족하여향후추가적인검증이필요하다. 9. 약물치료 1) 단백분해효소억제제비정상적으로활성화된소화효소에의한자가소화의진행을막고혈액응고인자를억제하여미세순환을회복시키기위하여 aprotinin, gabexate, ulinastatin 등의다양한단백분해효소억제제 (protease inhibitor) 치료가시도되어왔다. 하지만치료성적은기대에미치지못하였는데, 이는단백분해효소억제제가효과를발휘하기위해서는질병경과의극초기에투여되어야하지만현장에서는환자가내원하여투약되기까지상당한시간이지체되고, 실제로투여된이후에도미세순환의장애로인하여충분한췌장내농도에도달하지못하기때문으로이해되고있다. 81,82 이러한문제점을타개하기위하여일본을중심으로단백분해효소억제제의지속적국소적동맥내주입 (continuous regional intra-arterial infusion, CRAI) 이시도되고있는데, 여러소규모연구에서복통의강도, 혈중 C-반응단백및 IL-6/IL-10의비율, SIRS 및감염성췌장괴사의발생, 입원기간, 사망률등을감소시키는것으로보고되었다 또한 Takeda 등 83 은증상발생 48시간이내에항생제투여와함께 CRAI를시작한경우에감염성췌장괴사및사망률을감소시킨다고하였다. 하지만전국적으로 1,000명이상의환자가등록되었던경향분석연구 (propensity score analysis) 에서는긍정적효과없이입원기간및비용의증가가나타났다. 87 또한현실적으로췌장을공급한혈류가감소되어있는상황에서도관의적절한삽입은기술적으로용이하지않아, 약 1/5의환자에서는실패하는것으로보고되었다. 86 2) 항산화제산화스트레스 (oxidative stress) 가급성췌장염의발병기전에중요한역할을한다는사실은여러동물실험을통해잘알려져있다. 82 이에셀레니움 (selenium), 비타민 C, N-acetyl cysteine, 알파토코페롤 (α-tocopherol), 베타카로틴 (β-carotene), 카르니틴 (carnitine), caffeic acid phenethyl ester 등 각종항산화제의단독혹은복합투여가시도되었으나, 일부지표에있어서의긍정적영향이관찰되었을뿐전반적인예후향상에미치는효과는입증되지않았다 단, 글루타민은예외적인데, 여러가지항산화제를시험하였던 11개의무작위대조연구를대상으로한최근의메타분석은글루타민만이뚜렷한합병증과사망률개선효과를나타내었다고언급하였다. 91 글루타민을시험하였던 12개의무작위대조연구의 505 명의환자를대상으로한메타분석에서도글루타민의정맥투여는입원기간을단축시키지는못하였지만사망률과감염성합병증의발생을감소시키는것으로나타났다. 92 하지만장관투여의경우에는이러한효과가관찰되지않았는데, 이는글루타민이장관및간에서분해되어정맥투여한경우보다혈중농도가낮기때문으로보인다. 93 3) 췌장분비억제제각종위장관호르몬이나펩티드의작용을억제하는소마토스타틴 (somatostatin) 과합성유도체인옥트레오타이드 (octreotide) 치료가시도되었지만 2개의메타분석에서뚜렷한효과는입증되지않았다. 94,95 하지만최근중국에서 236명의중증질환이예측되는환자와 136명의중증급성췌장염을대상으로시행된무작위대조연구에서고용량 (3일간 50 g/hr+4일간 25 g/hr) 옥트레오타이드투여군은저용량 (7일간 25 g/hr) 군또는대조군에비하여중증으로의진행을억제하거나부분적으로중증질환을완화시키는것으로나타났다. 96 이러한고용량투여의효과는다른연구에서도관찰되었는데, Wang 등 97 은 306명의환자를대상으로대조군, 소마토스타틴 (10일간 250 g/hr) 단독투여군, 소마토스타틴및단삼 ( 丹蔘, Salvia miltiorrhiza) 병용투여군으로나누어시행된무작위대조연구에서소마토스타틴이투여된환자는 tumor necrosis factor (TNF)-, IL-6, IL-10, acute physiology and chronic health evaluation (APACHE) II 점수, 패혈증및다장기부전의발생, 사망률등이유의하게낮았다고보고하였다. 또한 Yang 등 98 은 161명의비만한경증의급성췌장염환자를대상으로한연구에서 3일간 50 g/hr의옥트레오타이드투여는 TNF- 및 IL-6의혈중농도를낮추고중증으로의진행을예방하였다고하였다. 하지만 Wang 등 97 과 Yang 등 98 의연구의경우중증질환의정의가모호하고대상환자군이균질하지않아소마토스타틴이나옥트레오타이드치료의확실한근거로제시되기에는부족할것으로보인다. 82 4) 기타약물이외에도비스테로이드성소염진통제 (NSAID), 99 platelet activation factor (PAF) 억제제, 100 activated protein C 101 등도시도되었으나뚜렷한효과는입증되지않았다. 최근에 pentoxifylline을투여하여다장기부전의발생에있어가장중요한사이토카인중하나인 TNF- 를억제하여중증의급 Vol. 66 No. 3, September 2015

6 140 이준규. 급성췌장염치료의최신지견 성췌장염환자의중환자실및전체재원일수를감소시킬수있었다는파일럿연구결과가발표되어향후대규모연구에대한추시가필요하다. 102 결 론 통증조절, 수액요법, 영양공급등보존적치료가급성췌장염치료의기본이다. 특히높은사망률을보이는중증의경우에는초기사망을막기위한다장기부전에대한집중적치료와함께후기사망을예방하기위하여감염등합병증의발생여부를집중적으로관찰하고필요한경우에는적절한조치를취하여야한다. 담석성급성췌장염의경우에는 ERCP를통해환자의상태를극적으로회복시킬수있는데, 적응증등구체적사항에대해서는추가적논의가필요하다. 병태생리학에기반한여러가지시도가있었지만아직까지효과가입증된약물치료는없으므로향후지속적인연구가필요하다. REFERENCES 1. Meng W, Yuan J, Zhang C, et al. Parenteral analgesics for pain relief in acute pancreatitis: a systematic review. Pancreatology 2013;13: Johnson CD, Besselink MG, Carter R. Acute pancreatitis. BMJ 2014;349:g American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2012;116: Baillargeon JD, Orav J, Ramagopal V, Tenner SM, Banks PA. Hemoconcentration as an early risk factor for necrotizing pancreatitis. Am J Gastroenterol 1998;93: Wall I, Badalov N, Baradarian R, Iswara K, Li JJ, Tenner S. Decreased mortality in acute pancreatitis related to early aggressive hydration. Pancreas 2011;40: Warndorf MG, Kurtzman JT, Bartel MJ, et al. Early fluid resuscitation reduces morbidity among patients with acute pancreatitis. Clin Gastroenterol Hepatol 2011;9: Gardner TB, Vege SS, Chari ST, et al. Faster rate of initial fluid resuscitation in severe acute pancreatitis diminishes in-hospital mortality. Pancreatology 2009;9: Gardner TB, Vege SS, Pearson RK, Chari ST. Fluid resuscitation in acute pancreatitis. Clin Gastroenterol Hepatol 2008;6: de-madaria E, Soler-Sala G, Sánchez-Payá J, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol 2011;106: Zhang W, Kim D, Philip E, et al; Gluco VIP study. A multinational, observational study to investigate the efficacy, safety and tolerability of acarbose as add-on or monotherapy in a range of patients: the Gluco VIP study. Clin Drug Investig 2013;33: 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 (Engl) 2010;123: Haydock MD, Mittal A, Wilms HR, Phillips A, Petrov MS, Windsor JA. Fluid therapy in acute pancreatitis: anybody's guess. Ann Surg 2013;257: 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: 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: 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-e Phillips CR, Vinecore K, Hagg DS, et al. Resuscitation of haemorrhagic shock with normal saline vs. lactated Ringer's: effects on oxygenation, extravascular lung water and haemodynamics. Crit Care 2009;13:R Zhao G, Zhang JG, Wu HS, et al. Effects of different resuscitation fluid on severe acute pancreatitis. World J Gastroenterol 2013; 19: 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: Wang MD, Ji Y, Xu J, Jiang DH, Luo L, Huang SW. Early goal-directed fluid therapy with fresh frozen plasma reduces severe acute pancreatitis mortality in the intensive care unit. Chin Med J (Engl) 2013;126: Gardiner KR, Kirk SJ, Rowlands BJ. Novel substrates to maintain gut integrity. Nutr Res Rev 1995;8: Versleijen MW, Oyen WJ, Roelofs HM, et al. Immune function and leukocyte sequestration under the influence of parenteral lipid emulsions in healthy humans: a placebo-controlled crossover study. Am J Clin Nutr 2008;87: Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev 2010;(1):CD Sun JK, Mu XW, Li WQ, Tong ZH, Li J, Zheng SY. Effects of early enteral nutrition on immune function of severe acute pancreatitis patients. World J Gastroenterol 2013;19: Bakker OJ, van Brunschot S, van Santvoort HC, et al; Dutch Pancreatitis Study Group. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. N Engl J Med 2014; 371: Singh N, Sharma B, Sharma M, et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. Pancreas 2012;41: Eatock FC, Chong P, Menezes N, et al. A randomized study of early nasogastric versus nasojejunal feeding in severe acute The Korean Journal of Gastroenterology

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