The Korean Journal of Gastrointestinal Endoscopy Room D ERCP in Patients Taking Anticoagulants or Antiplatelet Agents 부산대학교의과대학내과학교실 서론 내시경적역행성담췌관조영술 (endoscopic retrograde cholangiopancreatography, ERCP) 은췌담도질환의진단과치료에가장중요한검사로최근여러검사방법들과부속기구들의발전으로인해점차그영역이넓어지고있고, 특히담관담석과수술적치료가불가능한췌담관암환자에서가장중요한치료방법이다. 최근의췌담도환자들은과거에비해고령화되는추세여서다양한질환을동반하는경우가많고, 특히고혈압, 당뇨병과같은질환으로인한심장질환및뇌혈관질환, 말초혈관질환의유병률이증가하여예방적목적이나치료적목적으로항응고제및항혈소판제제의사용이많은실정이다. 이러한약제를복용하는환자에서치료적 ERCP는약물중단으로인한혈전색전증의위험과약물사용으로인한출혈위험두가지문제를일으킬수있다. 시술자는이러한상황에서두가지위험을피하면서성공적인내시경시술이되도록정확한판단을해야하지만, 이러한위험성을예측하기에는환자의질환이나상태, 사용하는약제등이너무나다양해서일률적인지침을따르기가어려운실정이다. 그래서의사마다자신의경험과지식에따라진료방식의차이가나며, 현재제시된여러가이드라인들조차도통일된지침을보여주지못하고있다. 이러한가이드라인의제정은후향적연구결과와약물의약리작용에근거하여이루어져있어지역별로차이점을보여주고있다. 본고에서는항응고제및항혈소판제제를복용하는환자에서의성공적인 ERCP에도움이되도록여러나라에서제정된가이드라인과이들의차이점을분석하고항응고제및항혈소판제제를살펴보았다. Guideline 1. American Society for Gastrointestinal Endoscopy, 2002 (Table 1), 1 2005 (Table 2) 2 2. Japan Gastroenterological Endoscopy Society, 2005 (Table 3, 4) 3 3. French Society of Digestive Endoscopy, 2006 (Table 5) 4 4. British Society of Gastroenterology, 2008 (Fig. 1, Table 6 8) 5 먼저항응고제와항혈소판제제를사용하는환자에서내시경가이드라인을살펴보면, 2002년과 2005년에미국소화기내시경학회에서제정하였고, 2005년에일본소화기내시경학회에서, 2006년프랑스소화기내시경학회에서, 2008년에영국소화기학회에서제정하여실제임상에적용되고있어이를정확히숙지해야해야하며이를토대로우리나라실정에맞는가이드라인제정이필요한실정이다. 1. 위험군의분류 1) 시술에따른출혈위험군의분류 : 출혈의위험성에따라 high-risk procedures와 low-risk procedures로분류할수있으면 high-risk procedures에는용종절제술, 내시경적유두부괄약근절개술 (endoscopic sphincterotomy, EST) 위장관협착의내시경적확장, 정맥류치료, 경피내시경적위루술, 내시경초음파를통한세침흡입술 (endoscopic ultrasound with fine needle aspiration, EUS with FNA), 내시경적점막절제술이나점막하박리술등이포함된다. Low-risk procedures에는조직검사를포함한진단목적의위장관내시경및 ERCP, EUS, EST를시술하지않는담췌관스텐트등이해당된다. 2) 혈전색전증위험군의분류 : 두가지경우로나눌수있는데항응고제복용군과항혈소판제제복용군으로나눌수있다. 먼저항응고제복용군에서약물중단시혈전색전증의위험성에따라고위험군와저위험군으로나눌수있으며, 고위험군은인공승모판막, 심방세동을동반한인공심장판막과승모판협착증, 3개월이내에발생한혈전색전증, thrombophilia syndromes이해당되며저위험군은인공대동맥판막, 생체인공판막, 심장판막질환이없는심방세동, 3개월이전에발생한혈전색전증이해당된다. 다음으로항혈소판제제복용군에서약물중단시혈전색전증의고위험군은 12개월이내약물방출관상동맥스텐트를삽입한경우, 1개월이내비막부착성금속관상동맥스텐트를삽입한경우이며, 저위험군은관상동맥스텐트를삽입하지않은허혈성심질환, 뇌혈관질환, 말초혈관질환이다. 이러한위험군의분류는동서양의가이드라인이크게다르지않아어느정도일치한다고판단된다. Vol. 39 (Suppl 1), 2009 (251-258) 251
Table 1. Acute Gastrointestinal Hemorrhage in the Anticoagulated Patient (American Society for Gastrointestinal Endoscopy, 2002) 1 Procedure risk High Low Condition risk for thromboembolism High Low Discontinue warfarin 3 5 days before Discontinue warfarin 3 5 days before procedure. procedure. Consider heparin while Reinstitute warfarin after procedure INR is below therapeutic level change in anticoagulation. Elective procedures should be delayed while INR is in supratherapautic range Procedure risk High-risk procedures Low-risk procedures Polypectomy Biliary sphincterotomy Pneumatic or bougie dilation PEG placement Endosonographic guided fine needle aspiration Laser ablation and coagulation Treatment of varices High-risk conditions Atrial fibrillation associated with valvular heart disease Mechanical valve in the mitral position Mechanical valve and prior thromboembolic event Diagnostic EGD±biopsy Flex sig±biopsy Colonoscopy±biopsy ERCP without sphincterotomy Biliary/pancreatic stent without endoscopic sphincterotomy Endosonography without fine needle aspiration Enteroscopy Condition risk Low-risk conditions Deep vein thrombosis Uncomplicated or paroxysmal nonvalvular arterial fibillation Bioprosthetic valve Mechanical valve in the aortic position Aspirin and other NSAID use In the absence of a pre-existing bleeding disorder, endoscopic procedures may be performed in patients taking aspirin or other NSAIDs. The decision to reverse anticoagulation and the extent of anticoagulation reversal should be individualized, weighing the risk of thromboembolism against the risk of continued bleeding. A supratherapeutic INR may be corrected with infusion of fresh frozen plasma. Correction of the INR to 1.5 2.5 permits effective endoscopic diagnosis and therapy. Reinstitution of antiocoagulation should be individualized. Recommendations for the management of anticoagulation, aspirin and NSAID use in patients undergoing endoscopic procedures based on the relative risks of the procedure and underlying condition. 2. 위험군에따른권고사항 1) Low-risk procedure : low or high risk condition: 서양가이드라인에서는환자의위험도와관계없이약물의조정이필요없다고권고하고있으나단 warfarin 복용시에는 international normalized range (INR) 을확인하여치료범위를초과하지않는지확인해야하는데, 먼저내시경검사 1주일전 INR을측정하여치료범위안에들면평소용량을복용하고치료범위를초과하였지만 5 미만인경우는치료범위안으로돌아올때까지용량을감소시킨다. INR이 5 이상인경우는내시경검사를연기하고해당과로연락을하라고권고하고있다. 5 일본의가이드라인에서항응고제의경우는저위험군인경우에시술 3 4일전부터 warfarin 복용을중지하고가능하면시술전 INR을 1.5 이하로낮출것과고위험군인경우에 heparin 사용을권고하고있고시술후출혈소견이낮다고판단되면재 복용을권고하고있다. 그리고항혈소판제제인경우는아스피린은 3일전중단, ticlopidine은 5일전중단, 아스피린과 ticlopidine 동시복용시에는 7일전중단과고위험군에서는 heparin 사용을권고하고있지만다시복용하는시기에대한언급은없다. 3 2) High-risk procedure: low risk condition: 미국과영국의가이드라인에서항응고제의경우는시술 3 5일전 warfarin 을중단하고시술전 INR이 1.5 미만을확인한후시술을시행하고시술당일저녁부터재투여하라고권고하고있다. 항혈소판제제의경우는시술 7 10일전부터 clopidogrel이나 ticlopidine을중지하고재투여는시술다음날부터투여하라고권고하고있다. 단아스피린의경우는계속적인복용이나 clopidogrel 이나 ticlopidine을중지하는경우에추가로투여할것을권고하고있다. 일본의가이드라인에서항응고제나항혈소판제제의경우는 252 The Korean Journal of Gastrointestinal Endoscopy
Table 2. Management of Low-molecular-weight Heparin and naspirin Antiplatelet Agents for Endoscopic Procedure (American Society for Gastrointestinal Endoscopy, 2005) 2 Procedure risk High Low Reinstitution of LMWH should be individualized Management of LMWH in patients undergoing endoscopic procedures Recommendation Consider discontinuation at least 8 h before procedure change in therapy Management of antiplatelet medication (clopidogrel or ticlopidine) in patients undergoing endoscopic procedures Procedure risk Recommendation High Consider discontinuation 7 10 d before procedure Low change in therapy Patients on combination therapy (e.g., clopidogrel and aspirin) may be at an additional increased risk of bleeding For acute GI hemorrhage in the patient in clopidogrel or ticlopidine, the decision to transfuse platelets should be individualized, usually weighing the risk of an acute cardiovascular event against the risk of continued bleeding Reinstitution of clopidogrel or ticlopidine should be individualized High-risk procedures Polypectomy Biliary sphinterotomy Pneumatic or bougie dilation PEG placement EUS-guided FNA Laser ablation and coagulation Treatment of varices Procedure risk Low-risk procedures Diagnostic EGD±biopsy Flexible sphincterotomy±biopsy Colonoscopy±biopsy ERCP without endoscopic sphincterotomy Biliary/pancreatic stent without endoscopic sphincterotomy EUS without FNA Enteroscopy Table 3. Management of Anticoagulant (warfarin) for Endoscopic Procedures (Japan Gastroenterological Endoscopy Society, 2005) 3 Low procedural risk High procedural risk INR, international normalized ratio. Low-condition risk of thromboembolic event Discontinue 3 4 days before procedure Start at little rebleeding risk Check of INR 1.5 before procedure is desirable Discontinue 3 4 days before procedure Start at little rebleeding risk Check of INR 1.5 is mandatory High-condition risk of thromboembolic event Discontinue 3 4 days before procedure Start at little rebleeding risk Check of INR 1.5 before procedure is desirable Consider heparin Discontinue 3 4 days before procedure Start at little rebleeding risk Check of INR 1.5 before procedure is mandatory Consider heparin low-risk procedure의권고안과유사하나시술전 INR을반드시 1.5 이하로낮출것을권고하고있다. 3) High-risk procedure: high risk condition: 미국과영국의가이드라인에서항응고제의경우는시술 3 5일전 warfarin을중단하고 heparin이나 low molecular weight heparin (LMWH) 사용하는 bridging anticoagulant therapy 을권고하고있으며 heparin과 LMWH을각각시술 4 6시간전, 8시간전사용을중단하고출혈이없으면시술후 6 8 시간뒤재사용한다. Warfarin은시술당일저녁부터재투여를시행하며 LMWH 은적절한 INR로회복될때까지유지하라고권고하고있다. 항혈소판제제의경우는심장전문의와상의한뒤만약약물방출관상동맥스텐트삽입이 12개월이상지난경우나비피막형관상동맥스텐트의경우에, 시술 7 10일전투여를중단하고반드시아스피린을투여를권고하고있다. 단시술이반드시필요한경우에는약물방출관상동맥스텐트삽입이 6개월이상지났다면일시적으로중단할수있으며재투여는시술다음날부터시행한다. 프랑스의가이드라인은항혈소판제제중단시에는 flurbiprofen이나 LMWH을대체약제로사용하고시술하루 Vol. 39 (Suppl 1), 2009 (251-258) 253
Table 4. Management of Antiplatelet Agents for Endoscopic Procedures (Japan Gastroenterological Endoscopy Society, 2005) 3 Low and high procedural risk Extremely high procedural risk Low-condition risk of thromboembolic event Discontinue 3 days before procedure for aspirin alone Discontinue 5 days procedure for ticlopidine alone Discontinue 7 days before procedure for aspirin and ticlopidine description for start Discintinue 7days before procedure for aspirin Discontinue 10 14 days before procedure for ticlopidine description for start High-condition risk of thromboembolic event Discontinue 3 days before procedure for aspirin alone Discontinue 5 days before procedure for ticlopidine alone Discontinue 7 days before procedure for aspirin and ticlopidine Consider heparin and hydration description for start Discontinue 7 days before procedure for aspirin Discontinue 10 14 days before procedure for ticlopidine Consider heparin and hydration description for start Table 5. Adapting the Treatment to Situations (French Society of Digestive Endoscopy, 2006) 4 NSAID, aspirin VKA Other antithrombotics Oral gastroscopy +/ biopsies Rectosigmoidoscopy +/ biopsies Colonoscopy without polypectomy +/ biopsies Diagnostic EUS ERCP without sphincterotomy +/ biopsies Enteroscopy +/ biopsies Colonoscopy with polypectomy ERCP with endoscopic sphincterotomy Gastic macrobiopsy and gastric polypectomy Mucosectomy, ampullectomy Laser photodestruction and photocoagulation Treatment of oesophageal or gastric varices Haemostatic procedures on vascular lesions EUS-FNA and EUS-guided therapy (e.g., drainage procedures) Percutaneous gastrostomy Dilatation of digestive stenosis Metal digestive prostheses insertion without dilatation Nasal gastroscopy, possible without stopping or replacing antithrombotic treatment;, possible without stopping or replacing treament if INR is not excessive;, replacement or withdrawal of antithrombotic treatment necessary except in special cases. 전중단할것을권고하고있다. 일본의가이드라인에서항응고제나항혈소판제제의경우는 low-risk procedure 의권고안과유사하나시술전 INR을반드시 1.5 이하로낮출것과 heparin 사용을권고하고있지만시술후재투여시기에대한언급은없어환자의상태에따라결정한다. 3. 동양과서양간의가이드라인차이점 6 소화기내시경영역에서항응고제와항혈소판제제에대한서양의가이드라인은아스피린복용중용종절제술이나 warfarin 복용중조직검사를권고하고있는데, 이는서양인은동 양인에비해혈전색전증의위험성이높다는데중점을두고제정된것이다. 하지만동양에서는, 약물중단으로인한혈전색전증의위험보다시술과연관된출혈의위험에좀더중점을두고있어동양과서양간의가이드라인은차이가있다. 동서양의소화기내시경의사의항응고제와항혈소판제복용환자에서의진료차이점을연구한논문에서는서양내시경의사들이시술과연관된출혈 (p=0.003) 과약물중단후혈전색전증 (p=0.016) 을좀더많이경험하였다. 동양내시경의사들은용종절제술시행 7일이상아스피린을중단하였고용종절제술후 1 3일뒤에재투여한반면서양내시경의사들은아스피린중 254 The Korean Journal of Gastrointestinal Endoscopy
Figure 1. Guidelines for the management of patients on warfarin or clopidogrel undergoing endoscopic procedures (British Society of Gastroenterology, 2008). 5 AF, atrial fibrillation; EMR, endoscopic mucosal resection; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; FNA, fine needle aspiration; INR, international normalised ratio; LMWH, low molecular weight heparin; PEG, percutaneous endoscopic gastroenterostomy; VTE, venous thromboembolism. Table 6. Risk Stratification of Endoscopic Procedures Based on Risk of Haemorrhage (British Society of Gastroenterology, 2008) 5 High risk Colonoscopic polypectomy ERCP with sphincterotomy Endoscopic mucosal resection or endoscopic submucosal dissection Endoscopic dilatation of strictures in the upper or lower GI tract Endoscopic therapy of varices Percutaneous gastrostomy Endoscopic ultrasound with fine needle aspiration Low risk Diagnostic procedures, with or without biopsy Biliary or pancreatic stenting Diagnostic endoscopic ultrasound This Table is adapted from the American Society for Gastrointestinal Endoscopy (ASGE) guideline on the management of anticoagulation and antiplatelet therapy for endoscopic procedures.1 ERCP, endoscipic retrograde cholangiopancreatography; GI, gastro-intestinal. Table 7. Risk Stratification for Discontinuation of Anticoagulant Therapy (British Society of Gastroenterology, 2008) 5 High risk Prosthetic metal heart valve in mitral position Prosthetic heart valve and atrial fibrillation Atrial fibrillation and mitral stenosis <3 months after venous thromboembolism Thrombophilia syndromes Low risk Prosthetic metal heart valve in aortic position Xenograft heart valve Atrial fibrillation without valvular disease >3 months after venous thromboembolism Vol. 39 (Suppl 1), 2009 (251-258) 255
Table 8. Risk Stratification for Discontinuation of Clopidogrel (British Society of Gastroenterology, 2008) 5 High risk Drug eluting coronary artery stents within 12 months of placement Bare metal coronary artery stents within 1 month of placement Low risk Ischaemic heart disease without coronary stents Cerebrovascular disease Peripheral vascular disease 단없이용종절제를시행하였다 (p<0.001). 결국서양에비해동양내시경의사들은 ASGE 가이드라인을잘따르지않았다는결과를보고하였다 (p<0.001). 이러한결과는서양의가이드라인이출혈의위험을증가시킨다고동양내시경의사들이믿고있기때문인데, 일부연구들에서동양인에서아스피린투여시대장점막출혈시간이증가된다고보고하여 7 일본에서는시술전 3일동안아스피린중단을권고하였다. 그리고동양내시경의사들은동양인보다서양인이좀더혈전색전증의위험이높다고믿기때문에혈전색전증의위험보다는출혈의위험에좀더비중을두는것같았다. 하지만혈전색전증은출혈에비해더사망률이높고, 서양인에비해뇌혈관계혈전증과같은중증인경우가동양인에서더높기때문에이러한약물의중단은신중해질필요가있다. 한국의보고에의하면 81명의내시경의사중 6명 (7.4%) 에서약물중단후혈전증을경험하였고 5명의환자 (83.3%) 에서뇌혈관계혈전증이발생하였다. 8 여기에서는 ERCP에대한논의는없었는데, 진단적 ERCP는진단적내시경검사로, EST를포함하는치료적 ERCP는 polypectomy에준해조사된것으로추측되어 ERCP 영역에서도비슷한가이드라인을사용했을것으로추측된다. 항응고제및항혈소판제 1. 항응고제 1) Warfarin: Warfarin은 vitamin K 길항제로혈액응고인자 (II, VII, IX, X) 의활성화를저해한다. 혈액응고를위해서는혈액응고인자의 glutamic acid의 carboxylation이필요한데 warfarin은 vitamin K의촉매작용을방해하여 carboxyglutamate 전환을억제하여정상적인혈액응고과정을억제한다. Warfarin은생물학적이용성이좋아경구섭취후 90분이지나면최고혈중농도에이르며반감기는 40시간이상이고한번투여로 120시간까지혈중에존재한다. 항혈전작용은복용후 6일이지나서나타나며항응고효과는 2일이지나야나타난다. 약중단후정상적인응고상태로회복되는기간은이론적으로는 2 4 일정도로알려져있다. 효과적인항응고효과는 INR이 2 3이적절하며, 1.5 미만인경우는정상인과비슷한출혈위험을보이며 6 이상 INR은출혈을야기할수있다. 2) Heparin and low-molecular weight heparin (LMWH): Heparin의항응고효과는 antithrombin III의기능을활성화시키 고 anti-xa activity로인해발생한다. LMWH은기존의 heparin 에비해단백결합이적어용량에따른항응고효과를예측할수있다. 그외 LMWH의장점은피하주사가가능하고, 기존의 heparin보다반감기가길고, 출혈경향이적으며, 혈소판감소증의발현빈도가낮고응고시간측정이필요없이몸무게에일정량을주입하므로입원이필요없다는점이다. Heparin 정맥주사시에는작용시간이 4 6시간까진지속되며 activated partial thromboplastin time (APPT) 로작용지속유무를측정가능하며, LMWH의작용시간은약 12시간까지지속될수있으나, 8시간이경과하면항응고작용이사라지는것으로보고되었다. 2. 항혈소판제 1) Aspirin과 NSAIDs: 아스피린은비가역적으로혈소판의 cyclooxygenase (COX) 를억제한다. 항혈소판작용은혈소판의 thromboxane A 2 (TXA 2) 를억제하여혈소판응집을방해하여나타난다. 위점막손상은 COX-1 경로가차단되어 prostaglandin E2 (PGE2) 와 prostacyclin (PGI2) 생성이억제되어발생한다. 아스피린은복용하고 30 40분이지나면혈중최고농도에이른고반감기는 15 20분으로매우짧지만비가역적으로혈소판의 COX를억제하여혈소판의생명이다할때까지응집능력을저해한다. 혈소판의생명이 7 10일정도로알려져있으므로약중단후시술가능한기간은 3 4일정도로생각된다. 아스피린에비해 NSAIDs는가역적으로 COX-1을억제하여반감기에따라차이가나겠지만항혈소판기능은일시적인것으로알려져있다. 4 NSAIDs는혈소판억제작용이 24시간이내로짧아이에따른조정이필요하다. 9 2) Adenosine diphosphate (ADP) receptor inhibitors (Clopidogrel, Ticlopidine): Clopidogrel과 ticlopidine은 thienopyridines 유도체로 adenosine diphosphate (ADP) 와혈소판막 ADP수용체의결합을비가역적으로억제하여혈소판응집을방해한다. 투여후간의 cytochrome P450에서활성화되어 3 5일뒤에항혈소판작용을나타낸다. Clopidogrel 은투약중단후 3 5일째에는혈소판기능이회복되지만완전한회복기간은 7 10일정도이다. 3) Phosphodiesterase inhibitors (Cilostazole): 작용기전은혈소판내의 cyclic AMP phosphodiesterase 활성을저해하여혈소판응집을억제하며반감기는 18시간정도로알려져있다. 4) Glycoprotein IIb/IIIa inhibitors (Abciximab, Eptifibatide, Tirofiban) 2 : GP IIb/IIIa receptor inhibitor는혈소판 256 The Korean Journal of Gastrointestinal Endoscopy
응집의최종단계인 GP IIb/IIIa receptor와 fibrinogen이결합하는것을억제하는주사제제이다. 중단후지속시간은 abciximab은 24시간, eptifibatide, tirofiban은 4시간동안지속되고항혈소판효과는혈소판수혈이나 desmopressin (DDAVP) 로일부회복이된다. 이들제제들은중증출혈위험도가높아일부에서만사용하고있으며아직까지소개할만한연구결과가없어정확한치료지침이없는상태이다. 2 5) Adenosine reuptake inhibitors (Dipyridamole) 2 : Adenosine uptake을억제하여항혈소판작용을나타내며 aspirin과복합제제로제조되어있다. 항혈소판작용은약해출혈의위험을증가시키지는않는다고알려져있어표준용량에서는내시경시술이가능해보이지만아직까지 high-risk procedure 군에서의안전성은알려져있지않다. 2 ERCP 검사시권고사항 일반적인사항을살펴보면 1) 항혈전치료가일시적이고내시경적시술이고위험군이며응급상황이아니라면내시경시술을연기한다. 2) 응급상황에서항혈전치료가중단되지않았거나조기에재투여가필요하다면출혈의위험성을최소화할수있는내시경시술을선택한다 ( 예, placement fo biliopancreatic prostheses without EST). 필요에따라서시술중 local hemostatic procedure를시행할수있으며항혈전치료억제효과를보이는약물길항제나수혈의사용을신중히고려해야한다. 3) 응급상황에서환자의혈전색전증의위험을알수없는경우에는고위험군으로간주하고치료한다. 4 현재구체적으로권고사항에언급된 ERCP 관련시술은살펴보면, low-risk procedures는 diagnostic ERCP, endoscopic retrograde biliary drainage or pancreatic drainage (ERBD or ERPD) without EST, ERCP with dilation of ampulla or bile duct이며 high-risk procedures는 EST, EUS with FNA라고언급되고있다. 그러나 needle knife fistulotomy (NKF)/precut papillotomy, large balloon dilation (LBD) with minor EST 등에대해서는구체적인언급은없지만넓은범주에 EST 군으로포함시킬수있어 high-risk procedure에포함시킬수있다. 1. Diagnostic ERCP 서양의가이드라인에서진단적 ERCP의경우는저위험군에해당되므로내시경시술시항응고및항혈소판치료는계속되어야한다. 하지만 selective cannulation of bile duct 실패율이 10 24% 이며 precut이나 fistulotomy를시행하기어려우므로항응고제및항혈소판제를복용중인환자에서는 low-risk procedure인 EUS나 MRCP를시행하는것이안전하다고생각되며이검사결과에따라치료적 ERCP를시행하는것이합리적이다. 2. ERBD or ERPD without EST, ERCP with dilation of ampulla or bile duct 응급상황에서항응고제나항혈소판제제를중단할시간적여유가없고다른대체가능한시술이없는상황에서시행하는방법으로경험이많은숙련자에의해시행하는것이시술의성공률을보장받을수있다. 그러나 endoscopic papillary balloon dilation (EPBD) 의안전성을보고한대부분의연구들은 10 mm 이하의확장을주로사용했으므로 10 mm 이상의확장은주의가필요하다. 3. EST 와연관된시술 EST나 LBD with minor EST, NKF/precut papillotomy이예상되는치료 ERCP는고위험군에해당되므로항응고제나항혈소판제제의중단이필요하다. EST는출혈이 2.0% 에서발생하고이중중증출혈은 0.5%, 출혈로인한사망률은 0.1% 로출혈의위험성이높다. 10 LBD with minor EST의경우는 EST 단독과유사한합병증을보이나출혈로인해사망한환자들이보고되고있으므로항응고제나항혈소판제제를복용하는환자에서무리한확장은위험할수있으며 NKF/precut papillotomy은출혈의위험이 5 6% 로 EST보다더높다고알려져있어주의를요한다. 서양의가이드라인에서항응고제는시술당일저녁부터재투여를권고하지만 EST 후 3일이내의항응고제를복용하면중증출혈의위험도가 10 15% 증가한다는보고가있으므로 10 시술당일저녁부터의 warfarin 투여는출혈의위험도보다혈전색전증의위험도가높다고판단되는경우에고려한다. 항혈소판제제인아스피린을복용중인환자에서 EST 시술이필요한경우에는혼란스러운점이많다. 앞에서언급한가이드라인을살펴보면동서양의차이가분명하여서양의가이드라인에서는아스피린복용에관계없이시술을시행하지만일본의가이드라인은반드시아스피린중단을권고하고있다. 이는참조한연구결과들의상반된결과로인한것임으로 10-14 이에대한통일된가이드라인이필요하며두연구에서는아스피린과 NSAIDs 복용환자에서 EST가출혈의위험성을증가시키지않는다고보고하였다. 10,15 4. EST 후발생한심각한출혈 시술전항응고제나항혈소판제제의복용사실을알고있었다면가이드라인에맞게시술시간을조절하는것이중요하지만응급상황이나복용사실을모르는상황에서시술을시행한후심각한출혈이발생했다면적절한조치가필요할것이다. 내시경지혈술과동시에약제를확인후항응고제나항혈소판제제의중단이필요하며, 항혈소판제제를복용하고있었을경우에혈소판수혈이나 DDAVP (desmopressin) 투여가적절한 Vol. 39 (Suppl 1), 2009 (251-258) 257
방법이될수있고항응고제제를복용하고있는경우에신선동결혈장을투여하여 INR을감소시키는것이적절한대처방법일것이다. Vitamin K는작용시간이 12 24 시간으로길기때문에 INR을감소시키는데시간이오래걸리므로투여하지않는것이바람직하다. 한연구에의하면 INR을 1.5 2.5 정도로유지하면내시경지혈치료의효과가일반인과동일하여내시경지혈술로소화관출혈을멈출수있다고하였다. 16 하지만지혈을위한이러한방법은환자의상황에따라달라질수있어지나친지혈술이혈전색전증의위험도를증가시킬수있다는점을고려해야겠다. 지혈후항응고제혹은항혈소판제의재투여시기역시마찬가지이다. 결론 최근의 ERCP의경향은진단적목적이아닌치료적목적으로사용되고있고 diagnostic ERCP는거의 EUS와 MRCP로대체되고있는실정이다. 특히항응고제나항혈소판제제를복용하고있는환자에서의 diagnostic ERCP는환자의안전이나시술자의부담을덜기위해서라도 EUS나 MRCP로대체되는것이바람직하다. Therapeutic ERCP는대부분이 EST를시행하는시술이많으므로시술전환자의약물복용력을철저히조사해야한다. 그리고항응고제및항혈소판제제의약리작용을숙지하여약물의중단시기를결정해야하며환자의상태에따라약물중단으로인한혈전색전증의위험을감소시키기위한추가적인조치를시행해야한다. 시술후에는출혈의위험과혈전색전증의위험을평가하여그중요도에따라약물의재투약을시도해야할것이다. 그러나이러한조치는동서양의가이드라인이다르고인종, 지역간의차이에따라서출혈과혈전색전증의위험이다룰수있으므로약물의중단과재사용으로인한위험과이득을신중히고려하여판단해야할것이다. 이러한판단은내시경시술자뿐아니라항응고제나항혈소판제제를처방하는주치의과긴밀한협진을통해이루어져야하며이를통해성공적인시술이될수있도록노력해야한다. 참고문헌 1. Eisen GM, Baron TH, Dominitz JA, et al. Guideline on the management of anticoagulation and antiplatelet therapy for endoscopic procedures. Gastrointest Endosc 2002;55:775-779. 2. Zuckerman MJ, Hirota WK, Adler DG, et al. ASGE guideline: the management of low-molecular-weight heparin and nonaspirin antiplatelet agents for endoscopic procedures. Gastrointest Endosc 2005;61:189-194. 3. Ogoshi K, Kaneko E, Tada M, et al. The management of anticoagulation and antiplatelet therapy for endoscopic procedures. Gastroenterol Endosc 2005;47:2691-2695 [in Japanese]. 4. Napoleon B, Boneu B, Maillard L, et al. Guidelines of the French Society for Digestive Endoscopy (SFED). Endoscopy 2006;38:632-638. 5. Veitch AM, Baglin TP, Gershlick AH, et al. Guidelines for the management of anticoagulant and antiplatelet therapy in patients undergoing endoscopic procedures. Gut 2008;57: 1322-1329. 6. Lee SY, Tang SJ, Rockey DC, et al. Managing anticoagulation and antiplatelet medications in GI endoscopy: a survey comparing the East and the West. Gastrointest Endosc 2008;67:1076-1081. 7. Nakajima H, Takami H, Yamagata K, et al. Aspirin effects on colonic mucosal bleeding: implications for colonic biopsy and polypectomy. Dis Colon Rectum 1997;40:1484-1488. 8. Lee SY, Chang DK, Park DI, et al. Multicenter survey on gastrointestinal endoscopic examination during anticoagulation or antiplatelet medications [abstract]. Korean J Gastrointest Endosc 2006;33(suppl 2):169-170. 9. McQueen EG, Facoory B, Faed JM. n-steroidal antiinflammatory drugs and platelet function. N Z Med J 1986; 99:358-360. 10. Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335: 909-918. 11. Shiffman ML, Farrel MT, Yee YS. Risk of bleeding after endoscopic biopsy or polypectomy in patients taking aspirin or other NSAIDS. Gastrointest Endosc 1994;40:458-462. 12. Hui AJ, Wong RM, Ching JY, et al. Risk of colonoscopic polypectomy bleeding with anticoagulants and antiplatelet agents: analysis of 1657 cases. Gastrointest Endosc 2004;59:44-48. 13. Komatsu T, Tamai Y, Takami H, et al. Study for determination of the optimal cessation period of therapy with antiplatelet agents prior to invasive endoscopic procedures. J Gastroenterol 2005;40:698-707. 14. Nelson DB, Freeman ML. Major hemorrhage from endoscopic sphincterotomy: risk factor analysis. J Clin Gastroenterol 1994; 19:283-287. 15. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 1991;37:383-393. 16. Choudari CP, Rajgopal C, Palmer KR. Acute gastrointestinal haemorrhage in anticoagulated patients: diagnoses and response to endoscopic treatment. Gut 1994;35:464-466. 17. 김유경. 혈액응고장애환자의안전한내시경. 대한소화기내시경학회지 2005;30(suppl 1):162-167. 18. 박선미. 고위험군에서의 ERCP (ERCP in high risk patients). 대한췌담도학회지 2008;13:182-188. 19. 장재영. 아스피린, 항혈소판, 항응고제복용환자의내시경검사. 대한소화기내시경학회지 2009;38(suppl 1):23-26. 258 The Korean Journal of Gastrointestinal Endoscopy