07-04 이대상

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1 eissn pissn Journal of Trauma and Injury Vol. 28, No. 1, March, 2015 Case Report 수혈관련급성폐손상이동반된외상환자에서체외막산화기의적용경험 성균관대학교의과대학삼성서울병원 1 중환자의학과, 2 외과 이대상 1,2, 박치민 1,2 - Abstract - Application of Extracorporeal Membranous Oxygenation in Trauma Patient with Possible Transfusion Related Acute Lung Injury (TRALI) Dae-Sang Lee, M.D. 1,2, Chi-Min Park, M.D., Ph.D. 1,2 1 Department of Critical Care Medicine, 2 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea The case of a patient with a transfusion-related acute lung injury (TRALI) to whom extracorporeal membrane oxygenation (ECMO) had been applied is reported. A 55-year-old male injured with liver laceration (grade 3) without chest injury after car accident. He received lots of blood transfusion and underwent damage control abdominal surgery. In the immediate postoperative period, he suffered from severe hypoxia and respiratory acidosis despite of vigorous management such as 100% oxygen with mechanical ventilation, high PEEP and muscle relaxant. Finally, ECMO was applied to the patients as a last resort. Aggressive treatment with ECMO improved the oxygenation and reduced the acidosis. Unfortunately, the patient died of liver failure and infection. TRALI is a part of acute respiratory distress syndrome (ARDS). The use of ECMO for TRALI induced severe hypoxemia might be a useful option for providing time to allow the injured lung to recover. [ J Trauma Inj 2015; 28: ] Key Words: Adult, Blood transfusion, Extracorporeal membrane oxygenation, Respiratory distress syndrome, Trauma I. 서론 수혈관련급성폐손상 (Transfusion related acute lung injury, TRALI) 은수혈후 6시간이내에, 호흡곤란증 상을동반한단순흉부방사선사진에서양측성폐침범이있는경우로정의되며, 1983년 Popovsky에의해명명되었다.(1,2) 다발성외상환자에서는많은출혈로인하여농축적혈구뿐만아니라신선동결혈장및혈소판의대량수혈이요 Address for Correspondence : Chi-Min Park, M.D., Ph.D. Department of Critical Care Medicine, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul , Korea Tel : , Fax : , dr99.park@samsung.com Submitted : November 25, 2014 Revised : December 11, 2014 Accepted : January 6,

2 Dae-Sang Lee, et al.: ECMO in the trauma patient with TRALI 구되는경우가많으며, 이로인한항원-항체반응에의한수혈관련급성폐손상이초래될가능성이더욱높아진다.(2) 다발성외상에서유발된급성호흡부전증후군에서의체외막산화기 (extracorporeal membranous oxygenation, ECMO) 의적용은 1972년 Hill 등 (3) 에의해처음으로보고되었으며, 2009년 Kuroda 등 (4) 은간절제후발생한수혈관련급성폐손상환자에서체외막산화기를적용하여성공적인치료경험을보고하였다. 국내에서는다발성외상에서의체외막산화기의적용이아직보편적이지않으며, 특히다발성외상에서대량수혈로인한수혈관련급성폐손상에서의체외막산화기의적용은아직국내에서보고된바가없다. 저자들은외상으로인한혈복강을주소로내원하여개복수술을시행받은 30대남자환자에서수혈후 6시간이내에발생한급성폐손상에서체외막산화기의적용을경험하였기에문헌고찰과함께보고하는바이다. II. 증례 37세남자환자가교통사고로 2차병원경유하여혈복강을주소로본원으로전원되었다. 과거력및가족력상특이사항은없었다. 응급실도착당시환자의복부는팽만되어있었으며, 내원당시활력징후는혈압 140/100 mmhg, 맥박수분당 148회, 호흡수분당 38회이었다. O 2 mask 10 L/min 에서 SpO 2 99% 이었으나, type 4 호흡부전 (respiratory failure) 으로기관삽관후인공호흡기를적용하였다. 환자의복부는지속적으로불러오고있었으며, 복강내압은 60 cm/h 2O 로측정되었고, 소변은나오지않았다. 전산화단층촬영상 Grade 3의간열상이있었지만조영제의누출소견은관찰되지않았다. 영상의학과와상의결과복강내의높은압력으로인하여조영제의누출이관찰되지않기때문에기술적으로혈관조영술및색전술은어려울것으로판단하였다. 환자의활력징후가불안정하여수술적치료를우선하고, 필요시혈관조영술및색전술을시행하기로결정하였다. 수술소견상복강내다량의혈종이있었으며, S4~S2에걸쳐너비 15 cm의열상이약 10 cm 깊이로관찰되었으며, S5에서도 3 cm의열상이관찰되었으며, 주문맥 (main portal vein) 과총간동맥 (common hepatic artery) 의손상은관찰되지않았다. 간외의다른복강내장기의추가적인손상은발견되지않았다. 간열상부위로지속적인출혈이관찰되었으며, 우선적으로간열상봉합및 Floseal (Baxter, CA, USA) 을도포후거즈패킹 (gauze packing) 을시행하였고, 임시복벽봉합 (temporary abdominal closure) 을시행후추가적인혈관조영술및색전술을시행하기로계획하였다. 수술전응급실에서체류하는동안은 RBC 5 unit, FFP 3 unit, 수술중에는 RBC 5 unit, FFP 3 unit, platelet 10 unit 이사용되었다. 수술종료즈음충분한일회환기량 Table 1. Hospital course of the arterial blood gas analysis and extracorporeal membranous oxygenation. In operative filed After 3 hours After 5 hours Post ECMO POD 1 POD 2 POD 3 POD 4 POD 5 (prior to ECMO) (ECMO D 2) (ECMO D 3) (ECMO D 4) (ECMO D 5) (ECMO D 6) WBC ( 10 3 /μl) NA Hemoglobin NA Platelet ( 10 3 /μl) NA ph pco2 (mmhg) po2 (mmhg) HCO3 (mmol/l) O2 saturation (%) Sweep gas (L/min) NA NA NA CO (L/min) NA NA NA ECMO: extracorporeal membrane oxygenation, CO: cardiac output, POD: postoperative day ph, pco2, po2, HCO3, O2 saturation in the arterial blood gas analysis Sweep gas, CO in the extracorporeal membranous oxygenation Sweep gas applied by pure medical O2. 35

- Journal of Trauma and Injury Vol. 28, No. 1 - A B Fig. 1. Chest radiograph of a TRALI patient, preoperative state (A), showing the bilateral infiltrates respiratory distress syndrome) 에합당한양측폐의침범이확인되었다 (Fig.

To supply adequate gas exchange, the patients was applied veno-veno extracorporeal membranous oxygenation. Deoxygenated blood was drained from right femoral vein.

3 - Journal of Trauma and Injury Vol. 28, No. 1 - A B Fig. 1. Chest radiograph of a TRALI patient, preoperative state (A), showing the bilateral infiltrates respiratory distress syndrome) 에합당한양측폐의침범이확인되었다 (Fig. 1). 심장초음파소견상에서는울혈성심부전이나심근경색의소견은관찰되지않았다. 기계환기 (FiO 2 1.0, Peak Inspiration pressure 40 mmh 2O) 를적용하는 Fig. 2. Schematic picture of ECMO in the patient with temporary abdominal closure. Fig. 2. To prevent abdominal compartment syndrome, the patient was applied temporary abdominal closure. To supply adequate gas exchange, the patients was applied veno-veno extracorporeal membranous oxygenation. Deoxygenated blood was drained from right femoral vein. Oxygenated blood which was passed by membrane filter was administrated to right internal jugular vein. (tidal volure) 이유지되며, 100% 의산소공급에도불구하고산소포화도가유지되지않았고, 중환자실로급히이동후시행한동맥혈가스검사상 ph 7.081의심한산증및저혈압 (67/54 mmhg in norepinephrine 1.5 μg/kg/min) 으로혈관조영술및색전술을위하여환자를혈관조영실로이송하는것은불가능하였다 (Table 1). 중환자실로이동후촬영한단순흉부방사선사진상에서급성호흡부전증후군 (Acute 데도불구하고 ph 6.931, PaO mmhg, paco mmhg로심한호흡성산증소견을보였으며, 환자의심폐순환보조를위하여체외막산화기 (Veno-Veno ECMO) 를적용하였다 (Fig. 2). 탈혈캐뉼라 (Drainage cannula) 는환자의우측대퇴정맥에, 송혈캐뉼라 (return cannula) 는우측경정맥에위치하였으며 (Fig. 2), 외상으로인한출혈소인이있어항응고제는사용하지않았다. 지속되는출혈로인하여중환자실에서재개복하여간열상이있는우측간의출혈을막기위하여우측간동맥을 bulldog arterial clamp로결찰하였다. 이후수혈요구량은점차줄어들었으며, 체외막산화기및지속적신대치요법을함께시행하면서환자의산소공급및이산화탄소제거가원활하게되었으며, 산증이개선되었고활력징후또한안정되었으며, 간단한의사소통도가능할정도로호전되었다 (Table 1). 수상이틀뒤이루어진 3번째복부수술에서우측간동맥을결찰하고있던 bulldog clamp를제거하였으며, 출혈이지속되는부분에대하여추가적인봉합및 floseal (Baxter, CA, USA) 를도포하였으며, 이후더이상의출혈은관찰되지않았다. 환자의수혈요구량은감소하였지만, 그동안의많은혈액및수액공급으로인하여장부종이심하여복벽을닫을수는없었다. 단순흉부방사선사진상양측폐는여전히심한양측성침범소견을보였으나, 체외막산화기를통한산소공급및이산화탄소교환은적절하게이루어지고있었다. 개복상태로체외막산화기를적용중인환자를치료함에있어서체위변동시에각별한주의를기울이는것이외에는따른특별한기술적인문제는 36

4 Dae-Sang Lee, et al.: ECMO in the trauma patient with TRALI 발생하지않았다. 수상후 4일째시행한혈액배양검사에서그람음성간균 (gram negative bacilli) 이동정되어 carbapenem의사용을지속하였다. 하지만, 초기우측간동맥결찰로인하여초래된간부전및그람음성간균에의한패혈성쇽으로회복하지못하고 3번째수술후 3일째다장기부전으로사망하였다. 사망후보고된혈액배양검사에서는 minocycline을제외한모든항생제에서저항을보이는 Acinetobacter baumannii를확인하였다. 환자의 injury severity score (ISS) 는 27점, revised trauma score (RTS) 는 6.613, trauma injury severity score (TRISS) 는 6.6% 이었다. III. 고찰수혈관련급성폐손상 (Transfusion related acute lung injury, TRALI) 은수혈이후 6시간이내에발생하는저산소혈증, 흉부방사선사진에서의양측성폐침윤, 저혈압, 거품이많은담 (frothy sputum), 열, 저혈압, 청색증, 기침, 빈맥그리고폐유순도의감소등의소견을보이는급성폐손상 (Acute lung injury, ALI/acute respiratory distress syndrome, ARDS) 이발생하는경우로, 수혈이외에급성폐손상을일으킬수있는폐렴, 쇽 (shock), 패혈증, 다발성외상, 뇌손상, 급성췌장염, 독극물중독등의유발요인이없으며, 순환혈장량과다 (circulatory overload) 또는심장질환의증거가없는경우로정의된다.(2,5,6) 반면, possibble TRALI는수혈이후 6시간이내에 TRALI와같은임상양상을동반하고순환혈장량과다 (circulatory overload) 또는심장질환의증거가없는상태로, 수혈이외에급성폐손상을유발할수있는유발요인이동반되어있는경우로정의된다.(2,6) 수혈관련급성폐손상에서보이는이러한임상증상은항원-항체반응으로호중구 (neutrophil) 에의한폐포내피세포 (lung alveori endotherial cell) 의손상으로인하여초래된급성폐손상 (Acute lung injury) 의결과이며급성호흡부전증후군의한분류이다.(7) 수혈관련급성폐손상의병태생리는혈액공여자의혈장에존재하는 HLA (Human leukocyte antigen) 또는 HNA (Human neutrophil antigen) 가혈액수여자의백혈구와반응하여폐의미세혈관에손상을일으키거나, 드물기는하지만혈액수여자의혈장에존재하는 HLA 또는 HNA가혈액공여자의백혈구와반응하여폐의미세혈관에손상을일으킨다는 antibody hypothesis으로대부분설명된다. 이러한항원-항체반응의결과로초기 TRALI에서는일시적인백혈구의감소가관찰되기도한다.(8) 하지만임상에서이러한일시적인백혈구감소는초기에일어나며곧회복하기때문에백혈구검사를임상에서확인하기는쉽지않다. 수혈관련급성폐손상의약 10% 정도에서는이러한백혈구에대한항원-항체반응이아니라 lysophosphatidylcholines에의하여 priming된호중구에의한폐미세혈관손상이발생한다는 active lipids theory 에의한것이다.(5,9,10) 아직까지수혈관련급성폐손상의병태생리는완벽하게설명되지못하고있으며, 그진단도혈액학적검사보다는임상적근거에따른진단이주를이루고있다. 대부분의수혈관련급성폐손상은추가적인산소공급을필요로하며, 때로는기계환기치료를필요로하기도한다.(2) 심한수혈관련급성폐손상의임상양상은급성호흡부전증후군의증상과유사하며, 대부분의경우에추가적인산소공급및인공호흡기의도움이있다면 96시간이내에호전을보인다. 아주심한급성호흡부전증후군에서체외막산화기를치료목적으로사용하듯이수혈관련급성폐손상으로아주심한저산소증이있을경우손상된폐가회복될때까지보전적목적으로체외막산화기를사용해볼수있다. 체외막산화기를적용함으로써고농도의산소로인한폐손상을줄일수있고, 최대흡기압 (peak inspiratory pressure) 를감소시킴으로써인공호흡기관련폐손상을예방할수있는이점이있다. 본증례는흉부외상이없는복부외상환자에서대량수혈후 6시간이내에발생한급성폐손상으로, 수혈이외에외상및수술이라는추가적인급성폐손상의유발요인이있으며, 수술직후시행한초음파검사상에서정상심장기능소견을보여심부전으로인한폐부종및혈장량과다공급에의한 TACO (Transfusion related cardiac overload) 를감별진단하여 possible TRALI의진단기준에합당하였다.(2,6) 또한수혈시작후 6시간이내에백혈구수치의갑작스러운감소도관찰되었다 ( /μl /μl, Table 1). 하지만이는대량실혈및대량수혈로인한혈장량희석에의한요소도배제할수없겠다. 하지만 TRALI 를진단함에있어이러한수혈초기의백혈구감소는진단에필수적인요소는아니다. 안타깝게도 HLA/HNA antibody에대한검사를시행시행못한것이아쉽지만, 임상적으로 possible TRALI 를진단할수있었다. 수혈관련급성폐손상의치료는항원-항체반응으로유발된폐포내피세포의손상이저절로회복되기를기다리는보존적인방법이다. 대부분의경우추가적인산소공급만으로도충분하지만, 기계환기를통한침습적인치료방법을사용하기도한다. 약물치료로는혈장량의과다공급에의한심장기능장애가있다면이뇨제가도움이되겠지만, 항원-항체반응에의한수혈관련급성폐손상의병인을고려한다면이뇨제는큰도움이되지않는다. 일부에서는급성호흡부전증후군에서의스테로이드의사용에착안하여스테로이드의사용을고려하기도하지만아직수혈관련급성폐손상에서의스테로이드에대한전향적임상시험연구는보고된바가없다. 대부분의경우에 96시간이내에보존적치료만으로도경과의호전을보이며, 인공호흡기치료를하였다할지라도대부분 48시간이내에기관발관이가능하고 4일이내에단순흉부방사선소견상 37

5 - Journal of Trauma and Injury Vol. 28, No. 1 - 정상소견으로돌아온다. 하지만저산소증과폐침윤이일주일까지도보고되기도하며, 사망률은 6~10% 정도로보고된다.(5) 본증례에서는대량수혈후수혈관련급성폐손상이발생하였고기계호흡만으로이환자에게적절한가스교환을공급할수없어체외막산화기를적용하여환자의가스교환을원할하게하였다. 하지만계속되는출혈과환자에게적용하고있는여러장비 ( 체외막산화기, 지속적신대치요법, 기계환기, 급속가온혈액주입기 ) 로인하여수술장으로이동하지못하고중환자실에서다시개복술을시행하였다. 체외막산화기 (ECMO) 의적용후환자의저산소증은교정되었으며, 지속적신대치요법을시행하여산증도교정할수있었다. 하지만수상후 4일째간부전및감염으로인하여환자의상세는나빠지기시작하였고수상후 5일째다장기부전으로사망하였다. 우리는초기외상환자에서대량수혈후발생한수혈관련급성폐손상 (Transfusion related acute lung injury, TRALI) 를치료하기위하여체외막산화기를적용하여환자의산소화를개선시켰으나, 안타깝게도감염과간부전으로사망하였다. 하지만, 외상환자에서의적극적인 ECMO 사용을통한환자생존을향상시킬수있는가능성을보았기에보고한다. REFERENCE 01) Popovsky MA, Abel MD, Moore SB. Transfusion-related acute lung injury associated with passive transfer of antileukocyte antibodies. Am Rev Respir Dis 1983; 128: ) Vlaar AP, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet 2013; 382: ) Hill JD, De Leval MR, Fallat RJ, Bramson ML, Eberhart RC, Schulte HD, et al. Acute respiratory insufficiency. Treatment with prolonged extracorporeal oxygenation. J Thorac Cardiovasc Surg 1972; 64: ) Kuroda H, Masuda Y, Imaizumi H, Kozuka Y, Asai Y, Namiki A. Successful extracorporeal membranous oxygenation for a patient with life-threatening transfusion-related acute lung injury. J Anesth 2009; 23: ) Popovsky MA, Moore SB. Diagnostic and pathogenetic considerations in transfusion-related acute lung injury. Transfusion 1985; 25: ) Kleinman S, Caulfield T, Chan P, Davenport R, McFarland J, McPhedran S, et al. Toward an understanding of transfusionrelated acute lung injury: statement of a consensus panel. Transfusion 2004; 44: ) Kopko PM, Popovsky MA, MacKenzie MR, Paglieroni TG, Muto KN, Holland PV. HLA class II antibodies in transfusion-related acute lung injury. Transfusion 2001; 41: ) Marques MB, Tuncer HH, Divers SG, Baker AC, Harrison DK. Acute transient leukopenia as a sign of TRALI. Am J Hematol 2005; 80: ) Silliman CC, Dickey WO, Paterson AJ, Thurman GW, Clay KL, Johnson CA, et al. Analysis of the priming activity of lipids generated during routine storage of platelet concentrates. Transfusion 1996; 36: ) Looney MR, Gropper MA, Matthay MA. Transfusion-related acute lung injury: a review. Chest 2004; 126:

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untitled 대한수혈학회지 : 제 22 권제 3 호, 2011 심부전환자에서수혈관련급성폐손상의진단 1 예 홍윤지 1 ㆍ김정아 1 ㆍ최규태 1 ㆍ이경훈 1 ㆍ박경운 1,2 ㆍ송정한 1,2 ㆍ한규섭 1 = Abstract = 서울대학교의과대학검사의학교실 1, 분당서울대학교병원진단검사의학과 2 Diagnosis of Transfusion-Related Acute Lung Injury