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대한소화기내시경학회지 2008;37(Suppl. 1):158-162 급성위정맥류출혈의치료선택 고려대학교의과대학소화기내과학교실 서연석 위정맥류는문맥압항진증환자의 20% 정도에서발생하며 2 년에 25% 정도에서출혈을하는등 1 식도정맥류 와비교하여보았을때그발생빈도및출혈위험성이낮으며간경변증환자의상부위장관출혈원인의 5 10% 정도를차지한다. 2 그러나위정맥류에서출혈을하면식도정맥류출혈에비해출혈이더심하고수혈요구량및사망률이더높다. 1,3 또한일단지혈이된후에도재출혈의가능성이식도정맥류출혈에서보다더높다 (89% vs. 34%). 4,5 위정맥류의특징 위정맥류는식도정맥류보다점막하층내더깊숙이존재하고, 대개식도정맥류보다혈관크기가더크고, 정맥류의혈류가식도정맥류에서와같이작은크기의정맥을거치는것이아니라커다란정맥으로직접유입되며, 항상산과펩신에노출된다. 6,7 또한, 식도정맥류는 hepatic venous pressure gradient (HVPG) 가 12 mmhg 미만인경우에는거의출혈하지않으며, 간경변증으로상승한문맥압을떨어뜨릴수있는경경정맥간내문맥-전신단락술 (transjugular intrahepatic portosystemic shunt, TIPS) 이약물적및내시경적치료에반응하지않는환자의지혈에효과적이다. 이와는달리위저부정맥류는 HVPG가 12 mmhg 미만일때도출혈할수있으며, TIPS가별로효과적이지않을수있다. 이처럼위정맥류가식도정맥류에비해더낮은문맥압의상태에서출혈을하는것은위정맥류환자에서문맥순환계와전신순환계사이의단락이자연적으로발생하는경우가 (60 85%) 6,8 식도정맥류환자들 (17 21%) 에서보다 6 더많다는점이일부기여하였을것으로생각된다. 또한위정맥류의크기가일반적으로식도정맥류보다크다는점도관여할것으로생각된다. 즉, 정맥류벽의장력 (tension) 은정맥류파열을결정하는중요한인자이며정맥류직경은정맥류의장력을결정하는인자들중하나이다. 그러므로정맥류내압력이동일하다면직경이작 은혈관은터지지않는반면직경이큰혈관은터질수있으며이것이위정맥류출혈환자에서식도정맥류출혈환자에서보다문맥압이더낮은이유일수있다. 9 위정맥류의분류 위정맥류는위식도정맥류 (gastrooesophageal varices, GOV) 와단독위정맥류 (isolated gastric varices, IGV) 로분류하며, GOV는다시식도정맥류에연결된정맥류가위소만곡 (lesser curvature) 을따라진행하는경우 (GOV1) 와식도정맥류와연결된정맥류가위대만곡 (greater curvature) 을따라위저부까지진행하는경우 (GOV2) 로나뉘며, IGV는독립된정맥류가위전부에있는경우 (IGV1) 와그외다은부위의십이지장또는위에서관찰되는경우 (IGV2) 로구분된다. 1 GOV1은분문부정맥류 (cardic varix) 라고도하며 GOV2와 IGV1은위저부정맥류 (fundal varix) 라고도한다. GOV1이가장흔하여전체위정맥류환자의 70% 를차지하며 GOV2 및 IGV1은각각 21% 및 7% 를차지한다. 출혈빈도는 IGV1 및 GOV2가각각 78% 및 55% 로 10% 정도인 GOV1 및 IGV-2에비해더높다. 1 GOV1에서의출혈이내시경적치료로지혈에성공할가능성이가장높다. 10 위정맥류의혈역동학적특징 위식도정맥류에서측부순환계는복강내및종격동에위치하며식도및분문부정맥류형성에기여하는 portoazygos venous system과후복강에위치하며주로위저부정맥류형성에기여하는 portophrenic venous system의두가지로구분할수있다. 11 즉, 문맥순환계의좌위정맥 (left gastric vein) 을통해발생하여식도정맥류를형성한후전신순환계의 azygos 및 hemiazygos vein으로흘러가는데비해위저부정맥류의경우에는 short and posterior gastric vein으로혈액이유입되어정맥류를형성한후위신단락등을통해전신순환계의 inferior phrenic vein으로 158

서연석 : 급성위정맥류출혈의치료선택 159 흘러간다. 11 한연구에따르면식도정맥류의혈류는 azygos 및 hemiazygos vein으로배출되고, 분문부정맥류 (GOV1) 는모두식도정맥류로배출된다. IGV의혈류는 85% 에서는위신단락으로, 10% 는 gastrophrenic shunt, 5% 는 gastropericardiac shunt를통해배출된다고하였다. 11 급성위정맥류출혈의치료 위정맥류출혈에대해내시경적경화요법 (endoscopic injection sclerotherapy, EIS), 내시경적정맥류결찰술 (endoscopic variceal ligation, EVL) 및내시경적정맥류폐쇄술 (endoscopic variceal obturation, EVO), TIPS 및역행성경정맥위정맥류폐색술 (balloon-occluded retrograde transvenous obliteration, BRTO) 등을시도할수있으나어떤치료가가장최선의치료인가는아직확실하게밝혀지지않은상태이다. 1. 내시경적경화요법 알코올이나 ethanolamine oleate 등을정맥류내에주입하면정맥류의내피손상및혈전증을유발하여정맥류를굳게하며식도정맥류출혈에서의지혈및식도정맥류제거에매우효과적인것으로알려져있다. 12 그러나위정맥류의경우식도정맥류에비해많은양의혈류가빠른속도로흐르기때문에정맥류내에서경화제가빠른속도로씻겨나가버리므로식도정맥류에비해많은양의경화제를사용하게되므로복통이나발열등의부작용을더자주유발할뿐아니라 5 치료효과도떨어진다. 13 보고자에따라 EIS의위정맥류출혈에대한지혈성공율을 60 100% 까지보고하기도하였으나 5,14,15 대부분 GOV1 환자가많이포함되어있으며, 위저부정맥류출혈만을보았을때에는지혈실패율이더높다. 14,16 한연구에따르면 GOV1의경우 EIS의지혈성공율은 85%, 출혈에의한사망률은 8% 에불과한데비해위저부정맥류의경우에는지혈성공율은 44% 에불과하였고출혈에의한사망률은 41% 로높았다. 17 또한, 재출혈율이 90% 에이를정도로매우높았다. 4 즉, EIS는 GOV1의급성출혈및재출혈예방에는효과적일수있으나, 위저부정맥류의경우에는지혈성공율이낮고재출혈율이높아적절하지않을것으로생각된다. 2. 내시경적정맥류결찰술 EVL은식도정맥류의지혈및출혈예방에매우효과적인치료방법이며, 위정맥류출혈에서도치료로이용되기도한다. 위정맥류직경이 2 cm 미만인경우에는일반적 인밴드를사용할수있으나정맥류직경이 2 cm 이상인경우에는 detachable snare를사용하는것이좋다. 18,19 그러나 EVO와비교하였을때지혈성공율은더낮고재출혈율은더높은것으로보고되었다. 20,21 대개위정맥류는식도정맥류에비해크기가크고더깊숙이위치하고있어정맥류를덮고있는층이두꺼워 EVL로정맥류를성공적으로결찰하기가어렵다. 22 EVL이 EVO에비해재출혈율이더높은이유는 EVO는 EVL보다더넓은부위의더깊은층에위치하는측부혈관까지폐쇄시키나 EVL은점막층및점막하층에위치하는측부혈관에만작용하기때문으로생각된다. 21 3. 내시경적정맥류폐쇄술 EVO에는 n-butyl-2-cyanoacrylate (Histoacryl), isobutyl-2- yanoacrylate (Bucrylate), thrombin 등이이용되며이들은정맥류내에서고형화되고결국주입후수주 ~ 수개월후 glue cast가떨어져나오면서궤양을형성한다. 이들중가장흔히이용되는 n-butyl-2-cyanoacrylate (NBCA) 는단량체 (monomer) 의형태로존재하다가수분과접촉하면수분내의 hydroxyl ion에의해중합반응 (polymerization) 이신속하게일어나단단한아크릴로변하여 10 위정맥류치료에많이이용된다. NBCA가혈액과접촉하면그즉시중합반응이일어나므로다루기가어려운데, 리피오돌과일정비율로혼합함으로써응고되는속도를조절할수있다. 보통은 NBCA와리피오돌을 1:1의비율 (0.5 cc :0.5 cc) 로혼합하나치료하려는정맥류의크기및정맥류내의혈류속도에따라비율을바꾸어사용할수있다. 즉, 정맥류가크고혈류가매우빠른경우에는 NBCA 가빠르게희석되어천자부위의출혈이있을수있으며, 이런경우리피오돌혼합비율을낮추거나리피오돌을혼합하지않고 NBCA만주입할수도있다. NBCA를리피오돌에너무과하게희석하면중합반응이즉시일어나지않고지연되면서 glue가위신단락을통해대정맥으로이동하여전신합병증을일으킬위험이높아지므로 NBCA 를 40% 미만으로희석하면안된다. 한연구에따르면이러한 glue의이동으로인한합병증을막기위해서는직경 12 mm 이상의 IGV1의경우에는 NBCA의희석비율을 62.5% 이상으로해야한다고하였다. 23 NBCA의중합반응이일어나굳으면주사침이 glue 내에서빠지지않을수있으므로 NBCA를주입한후즉시주사침을빼내야한다. 주사침을정맥류에서빼내는동안주사부위에조준하여용액을계속뿌려주는데, 카테터내강의폐쇄를막기위해증류수를빠른속도로통과시키는것이좋다. 이후카테터나생검겸자를이용하여

160 대한소화기내시경학회지 2008;37(Suppl. 1):158-162 정맥류를촉진하여딱딱하게고형화되지않은부분에는 NBCA를추가로주입한다. 남아있는정맥류가있는가를확인하기위해내시경적초음파검사 (endoscopic ultrasound, EUS) 나 pulsed Doppler를이용하기도한다. NBCA 를주입한후수주내지수개월후 glue cast를덮고있는점막이떨어져나가면서궤양이형성된다. 많은연구에서 NBCA를이용한 EVO가위정맥류출혈에서지혈성공율이 90% 이상으로매우효과적이라고보고하였다. 12,20,24-27 위정맥류에대한 EVL과 EVO의효과를비교한 RCT에서는 EVO가지혈 20 및재출혈예방에 20,21 더효과적이었다. EIS와비교하였을때에도초기지혈및정맥류폐쇄에더효과적이었다. 12 재출혈예방을위한위정맥류제거율은 75% 정도로알려져있다. 28 재출혈은정맥류가소실되지않고남아있는환자에서만나타나며대부분 EVO 후 1년이내에나타난다. 28 EVO의효과는위정맥류의모양에의해영향을받을수있어, 미만형위정맥류의경우국소형위정맥류에비해효과가더낮다. 29 4. 경경정맥간내문맥 - 전신단락술 몇몇연구에서 TIPS가급성위정맥류출혈환자에서지혈성공율 90% 이상으로지혈에효과적이며재출혈율도낮아위정맥류출혈에서도효과적인치료법임을시사하였다. 30,31 그러나 TIPS는위정맥류출혈에대한다른치료가실패하였을때의 2차적치료로간주되는데, 이처럼위정맥류에서 TIPS가큰관심을받지못하는이유는다음과같다. 식도정맥류는 HVPG가 12 mmhg 미만인경우에는출혈하지않으며, 식도정맥류출혈에대한내시경적치료에실패한경우 TIPS를통해문맥압을감소시켜주는것이지혈및재출혈예방에효과적인것으로알려져있다. 그러나위정맥류는 HVPG가 12 mmhg 미만에서도출혈할수있으며 TIPS는 HVPG가 12 mmhg 이상으로상승하지않은경우에는사망률감소에별도움이되지않을수있다. 32 즉, TIPS는위신단락을가지고있어문맥압상승이그리심하지않은위정맥류환자에서는큰효과를기대하기힘들다. 또한 TIPS에는다음과같은중요한약점이있다 : (1) 단락의협착이흔하여 TIPS 시행 1년이내에 60% 에서발생한다 ; 33 (2) TIPS를받은환자의 30 50% 에서간성뇌증이새로발생하거나기존의간성뇌증이악화되는데, 34,35 TIPS 시행전간성뇌증이있었거나 65세이상의고령인경우발생할위험이높다. 36 대부분의간성뇌증은 lactulose를이용한표준치료에잘반응하나 3 10% 에서는치료에잘반응하지않아단락의폐쇄가필요할수도 있다 ; 37,38 (3) TIPS를통해다량의문맥혈류가간정맥을통해우심방으로유입되므로심장의전부하를증가시켜심장질환이있는환자의경우심부전을유발할수있다. 39 그러므로시행전심장초음파검사를시행하여심박출율 (ejection fraction) 이적어도 55% 이상되는환자들에서만시행하는것이좋다 ; 40 (4) 문맥의혈류가대부분간으로가지않고단락을통해전신순환으로빠져나가므로간기능이현저히악화될수있다. 40 TIPS와복수천자의효과를비교한연구에서 Child-Pugh class C인환자의경우 TIPS군에서예후가더불량하였던결과가이와관련이있을수있다. 41 그러므로 Child-Pugh score가 11점이상인경우에는 TIPS를시행하지않는것이좋다. 38 5. 역행성경정맥위정맥류폐색술 BRTO는흔히사용되는경화제인 ethanolamine oleate 를이용하는방사선학적치료로서위신단락이있는 IGV1 환자의치료를위해개발되었다. 42 TIPS에비해덜침습적이고시술하기도더쉽다. 위저부정맥류가전신순환계로유입되는경로는 85% 에서위신단락, 10% 에서는위횡경막 (gastrophrenic) 단락, 5% 에서는위심막횡경막 (gastropericardiophrenic) 단락을통하며, 11 BRTO는위신단락이나위횡경막단락을통해시행할수있으므로 43 위저부정맥류환자의 95% 정도에서시행이가능하다. TIPS와비교하였을때지혈성공율과생존율모두 BRTO 군에서더높았으며, 1년내재출혈율은 TIPS군에서더높았다. 44 BRTO는다른치료법과는달리 HVPG 정도, 정맥류의크기및모양에관계없이효과적으로시행할수있다. 13 BRTO의단점으로는위신단락등이없는경우시행할수없다는점이외에도 BRTO 후상당수의환자에서문맥압이상승하며이로인해식도정맥류가악화될수있다는점이있다. 42 한연구에따르면 BRTO 후 1, 3 및 5 년후각각 27%, 58% 및 66% 의환자에서문맥압이상승하였다. 42 또한위정맥류의급성출혈에서응급치료로시행하기가쉽지않을수있다는점도큰단점으로작용한다. 13 결 위정맥류출혈에대한여러가지내시경적또는방사선학적치료법들이보고되어있으나아직어떠한치료가가장효과적일것인가는확실하지않은상태이다. 이를규명할수있는대규모전향적연구가하루속히시행되었으면하는바램이다. 론

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