133 소아외과 : 제 17 권제 2 호 2011 년 Vol. 17, No. 2, December 2011 체외막산소화요법을적용한선천성횡격막탈장치료의초기경험 울산대학교의과대학서울아산병원소아청소년병원소아외과 1, 소아흉부외과 2 김태훈 1 조민정 1 박정준 2 김대연 1 김성철 1 김인구 1 서 론 대상및방법 체외막산소화요법 (Extracorporeal oxygenation membrane, ECMO) 은질환자체를치료하는것은아니지만임상호전에필요한시간동안가스교환을도와주어추가적인기계환기유발성폐손상 (ventilatorinduced lung injury) 을최소화하면서회복에필요한시간을확보해주는치료법으로흡입산화질소요법및고주파진동환기법을포함한기존의치료에반응하지않는호흡부전을동반한선천성횡격막탈장에마지막이용되는치료방법이다 1,2. ECMO 를적용하여치료한선천성횡격막탈장환자들의초기임상경험을분석하여 ECMO를적용한환자의치료성적, 관련합병증, 치료과정상의고려점등을살펴보고자하였다. 본논문의요지는 2011 년 6 월제 27 회소아외과학회춘계학술대회에서구연되었음. 접수일 : 11/9/26 게재승인일 : 11 / 12 / 27 교신저자 : 김대연, 138-736 서울송파구아산병원길 86 서울아산병원소아외과 Tel : 02)3010-3961, Fax : 02)3010-6841 E-mail: kimdy@amc.seoul.kr 2008년 4월부터 2011년 2월까지서울아산병원소아외과에서 ECMO 를적용하여치료받은 12명의선천성횡격막탈장환자들의의무기록을후향적으로분석하였다. ECMO 적용의기준은다음과같다. 재태연령 34주이상이면서출생체중 2.0 Kg이상, 주요한염색체결손이없고뇌실내심각한출혈의증거가없어야하며산소공급지수 (Oxygenation index) 가 40 이상이면서기존의인공호흡기치료로환자의활력징후가유지되지않는환자들에게 ECMO (Medtronic Bio-console, Model 560, USA) 를시행하였다. 원심펌프 (centrifugal pump : Medtronic Bio-pump BPX 50, USA) 및산소공급기 (Oxygenator: Sorin group, Lilliput 2 ECMO, Italy) 등이시스템에포함되었고시술시행시초기의 5례에서는 veno arterial ECMO 를시행하였는데총경동맥과내경정맥을이용하였고카테터는환자의체표면면적및혈관의크기에따라다양한크기를사용하였다 ( 동맥 : DLP Pediatric One piece Arterial cannula 8~12Fr, Medtronic, USA,
134 소아외과제 17 권제 2 호 2011 년 정맥 : DLP Straight Single stage Venous cannula 8~14Fr, Medtronic, USA). 이후에는 veno venous ECMO 를시행하였으며이중도관 (Double lumen catheter 12Fr, Maquet, Germany) 을주로이용하였다. 유지기간중펌프의속도는일단환자몸무게와키로구한체표면면적에맞춰혈류량 (flow) 을계산한후분당회전수 (RPM) 를 2500 이하로유지하면서, inflow/outflow circuit pressure, 환자의활력징후및동맥혈가스분석결과를지속적으로살펴보며조절하였다. 특히 veno venous ECMO 인경우에는반드시 flow 100 % 를유지하지않아도충분한 support가가능하므로이를고려하여속도를조절하였다. 환자의혈전예방을위해 activated clotting time (ACT) 을매시간측정하여 180~200 초를목표치로하여헤파린을조절하며정맥으로지속투여하였다. 산소공급지수는다음과같이계산하였다 3. Oxygenation index (OI) = Mean Airway Pressure (MAP) Inspired Oxygen Concentration (FiO 2 ) 100 Partial Pressure of arterial O 2 (Pa O 2 ) 환자들의성별, 재태연령, 출생체중, 출생후 1분및 5분아프가점수 (Apgar score), 출 생후 ECMO 적용전까지동맥혈가스분석, 출생후 ECMO 적용시점, ECMO 적용이후선천성횡격막탈장수술까지의기간, ECMO 관련합병증, 선천성횡격막탈장의위치와수술방법, 관련합병증및생존율등을파악하였다. 결과환자들의남녀비는 9:3 였다. 12명모두산전진단된경우들이었고평균재태연령은 38.8 ± 1.7 주, 평균출생체중은 3031 ± 499 g, 평균 ECMO 시행나이는생후 29.9 ±28.9 시간이었다. ECMO 시행후선천성횡격막탈장을치료받고생존한환자가 4명이었고사망한환자가 8명이었다. 생존한환자들은평균 5분아프가점수는 8.25 ± 0.96 이었고출생이후부터 ECMO 적용전까지평균동맥혈 ph 7.258 ± 0.830, 평균동맥혈 PaCO 2 48.2 ± 7.9 였다. 사망한환자들은평균 5분아프가점수가 7.00 ± 1.20 (p=0.109), 출생이후부터 ECMO 적용전까지평균동맥혈 ph 7.159 ± 0.986 (p=0.073), 평균동맥혈 PaCO 2 64.8 ± 16.1 (p=0.109) 로통계적으로유의하지는않지만임상적으로나쁜결과들을나타내었다 ( 표 1). 생존한환자들은각각 Table 1. Comparison of Pre ECMO Variables Survivors (n=4) Nonsurvivors (n=8) P value Gestational age (wk) 38.9 ± 0.9 38.7 ± 2.1 0.808 Birth weight (kg) 2.95 ± 0.40 3.07 ± 0.56 0.507 Mean ph 7.258 ± 0.830 7.159 ± 0.986 0.073 Mean PaCO 2 48.2 ± 7.9 64.8 ± 16.1 0.109 Apgar score at 1 min 5.75 ± 2.22 5.00 ± 1.77 0.570 Apgar score at 5 min 8.25 ± 0.96 7.00 ± 1.20 0.109
김태훈외 : 체외막산소화요법을적용한선천성횡격막탈장치료의초기경험 135 4,5,6,7일의 ECMO 유지기간을보였으며사망한 8명중 4명은 ECMO 중단은성공했으나이후폐동맥고혈압이진행한경우였으며나머지 4명은 ECMO 중단을하지못하고사망한증례들이었다. 선천성횡격막탈장은 10명에서왼쪽에, 2명에서오른쪽에위치하였으며간이탈장된장기들에포함된증례들도왼쪽의경우 3례, 오른쪽의경우 1 례포함되어있었다. ECMO 관련합병증은우선카테터관련하여위치가부적절하거나혈류량이충분치못해서재수술을통해카테터삽입부위조정을시행한경우가 4례있었으며 3례에서총경동맥혹은내경정맥혈전증이발생하였는데 3례모두보존적치료로호전되었다. 횡격막탈장수술후출혈로개복내지개흉수술이필요했던경우가 3례있었는데수술소견상특별한출혈병소가발견된경우는없었다. 2례에서는복부구획증후군 (abdominal compartment syndrome) 이발생하여봉합하였던복부근막을열어주어야했다. 또한 1례에서뒷목부분에욕창이발생하였다. 횡격막탈장수술은초기 4례에서는 ECMO 적용후 3~4일후에시행하였으나그이후증례들은 ECMO 적용후만 1일전후에시행하였다. 횡격막탈장수술전에사망한 1명을제외한 11 명중 6명에서인공막 (patch) 을이용하여봉합수술을시행하였다. 고찰국내에서는아직까지도거의적용되지못하고있었지만, 심한선천성횡격막탈장의치료에 ECMO가꾸준히이용되어왔으며 최근다른치료법들의발전등에힘입어 ECMO 의적용이꾸준히감소하고있지만아직도그이용빈도가 15~40 % 에이른다고한다 4. ECMO를적용하여치료한선천성횡격막탈장환자들의치료성적은최근의논문들의보고에서약 50 % 의생존율을보이고있다. 몇몇논문들은환자들의생존과연관되어유의한영향을주는인자들을분석했는데, Seetharamaiah 등은 Congenital Diaphragmatic Hernia Study Group 에등록된 82개병원의 1063 명의 ECMO 치료를받은선천성횡격막탈장환자들을분석하였는데수술전 (presurgical) 인자들중에는재태연령, 출생체중, 5분아프가점수, 심한심장기형동반유무, 산전진단유무등이생존에유의한영향을주는인자들로분석되었고, 치료와관련하여서는 ECMO 적용기간이가장강력한치료결과예측인자였으며탈장수술시인공막구조물을사용한경우와폐복수술과관련해서교정수술때일차폐복 (primary closure of the abdomen) 을못했던경우가나쁜치료성적과유의하게연관된인자들로분석되었다 5. 또다른단일기관연구들에서는 ECMO 시행전가장낮았던동맥혈이산화탄소분압수치, 폐면적대머리둘레비율 (lung area to head circumference ratio, LHR), 탈장된장기들중간의포함유무, ECMO 사용중신장합병증발생유무등이환자의생존율에영향을주는인자들로분석되기도하였다 6-8. 저자들의임상경험에서는 12명의비교적적은수의환자를대상으로하여서생존율에영향을주는통계적으로의미있는연관인자는찾을수없었으나사망한환자
136 소아외과제 17 권제 2 호 2011 년 들에비해생존한환자들은 5분아프가점수, 수술전동맥혈평균 ph와이산화탄소분압수치에서통계적으로는의미있지않으나보다나은수치들을보여주어수술전환자상태를평가하고결과를예측할때주요한참고치가될수있을것으로생각되었다. 한편 ECMO를적용한선천성횡격막탈장의교정수술의시기에대하여아직까지확립된것이없는상태로 ECMO를적용한후빠른시기에수술하는경우출혈의합병증발생이증가하기때문에 ECMO 치료가끝난후혹은거의종료하는시점에수술을시행하는것이바람직하다는의견과 ECMO 를적용한후빨리수술하면 ECMO 사용기간을줄일수있고, ECMO 치료후시간이경과하면서발생하는전신부종이수술을어렵게하며특히일차폐복을어렵게하는단점을극복할수있어조기수술이바람직하다는의견이있다 4,9,10. 또한 ECMO 적용후수술을시행하지않고임상호전이되지않는경우들도적지않아수술의시기를잡기가더욱어려워지는단점을지적하기도한다. 저자들의경우상태가호전되어 ECMO 치료를끊고수술이가능했던경우는없었으며초기 4례에서는 ECMO 적용만 4일을전후로수술을시행하였으나전신부종이많이발생하여이후의 7례에서는 ECMO 적용후만 1일전후로수술을시행하였는데 ECMO 적용후조기수술이부종이없는상태에서보다수월하게수술이이루어질수있었다. 수술후출혈로재수술을시행한경우가초기 4례중 1례에서있었고이후 7례중 2례에서발생하였는데 3례모두재수술시뚜렷한출혈병소가발견되지 는않았다. 저자들은아직증례가많지않아정확하게평가하는것이어렵지만출혈의위험성이증가하지않는다면활력징후가안정된후조기에수술하는것이바람직할것으로판단하고있다. 저자들의초기경험에서는 12명의환자들중 4명의환자들이생존하였는데보다나은성적향상을기대하기위해환자선정의기준, ECMO 적용및중단의시기선정, 선천성횡격막탈장의교정수술의시기등전반적인환자치료지침 (protocol) 확립및경험축적이필요할것으로판단된다. 실제로 Antonoff 등은분만장에서부터흡입산화질소요법적용, 고주파진동환기법의조기사용여부를포함한환기법사용기준, ECMO 적용기준, ECMO 적용후수술시기등이포함된환자치료지침을도입한것이유의하게환자들의생존율향상에기여했다고보고하였다 11. 결 론 저자들은기존의치료로유지될수없는중증선천성횡격막탈장환자치료를위해 ECMO 를활용하여일부환자에서성공적으로치료할수있었다. ECMO 적용및중단, 탈장수술시기결정등에경험이축적되고체계적치료지침의마련함으로써성적향상을기대할수있을것으로판단된다. 참고문헌 1. Kattan J, Godoy L, Zavala A, Faunes M, Becker P, Estay A, Fabres J, Toso P,
김태훈외 : 체외막산소화요법을적용한선천성횡격막탈장치료의초기경험 137 Urzúa S, Becker J, Cerda J, González A: Improvement of survival in infants with congenital diaphragmatic hernia in recent years: effect of ECMO availability and associated factors. Pediatr Surg Int 77:671-676, 2010 2. Khan AM, Lally KP: The role of extracorporeal membrane oxygenation in the management of infants with congenital diaphragmatic hernia. Semin Perinatol 29:118-122, 2005 3. Bartlett RH, Gazzaniga AB, Toomasian J, Coran AG, Roloff D, Rucker R: Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure: 100 cases. Ann Surg 204:236-245, 1986 4. Sluiter I, van de Ven CP, Wijnen RM, Tibboel D: Congenital diaphragmatic hernia: still a moving target. Semin Fetal Neonatal Med 16:139-144, 2011 5. Seetharamaiah R, Younger JG, Bartlett RH, Hirschl RB: Congenital Diaphragmatic Hernia Study Group: Factors associated with survival in infants with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: a report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 44:1315-1321, 2009 6. Tiruvoipati R, Vinogradova Y, Faulkner G, Sosnowski AW, Firmin RK, Peek GJ: Predictors of outcome in patients with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation. J Pediatr Surg 42:1345-1350, 2007 7. Odibo AO, Najaf T, Vachharajani A, Warner B, Mathur A, Warner BW: Predictors of the need for extracorporeal membrane oxygenation and survival in congenital diaphragmatic hernia: a center's 10 year experience. Prenat Diagn 30:518-521, 2010 8. Hoffman SB, Massaro AN, Gingalewski C, Short BL: Predictors of survival in congenital diaphragmatic hernia patients requiring extracorporeal membrane oxygenation: CNMC 15 year experience. J Perinatol 30:546-552, 2010 9. Dassinger MS, Copeland DR, Gossett J, Little DC, Jackson RJ, Smith SD: Congenital Diaphragmatic Hernia Study Group: Early repair of congenital diaphragmatic hernia on extracorporeal membrane oxygenation. J Pediatr Surg 45:693-697, 2010 10. Congenital Diaphragmatic Hernia Study Group, Bryner BS, West BT, Hirschl RB, Drongowski RA, Lally KP, Lally P, Mychaliska GB: Congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation: does timing of repair matter? J Pediatr Surg 44:1165-1171, 2009 11. Antonoff MB, Hustead VA, Groth SS, Schmeling DJ: Protocolized management of infants with congenital diaphragmatic hernia: effect on survival. J Pediatr Surg 46:39-46, 2011
138 소아외과제 17 권제 2 호 2011 년 Extracorporeal Membrane Oxygenation in Neonates with Congenital Diaphragmatic Hernia: a Preliminary Experience Taehoon Kim 1, M.D., Min Jeng Cho 1, M.D., Jeong-Jun Park 2, M.D., Dae Yeon Kim 1, M.D., Seong-Chul Kim 1, M.D., In-Koo Kim 1, M.D. Division of Pediatric Surgery 1, Division of Pediatric Cardiac Surgery 2, Asan Medical Center Children s Hospital, University of Ulsan College of Medicine, Seoul, Korea Extracorporeal membrane oxygenation (ECMO) has been utilized in congenital diaphragmatic hernia (CDH) patients with severe respiratory failure unresponsive to conventional medical treatment. We retrospectively reviewed 12 CDH patients who were treated using ECMO in our center between April 2008 and February 2011. The pre ECMO and on ECMO variables analyzed included gestational age, sex, birth weight, age at the time of ECMO cannulation, arterial blood gas analysis results, CDH location, timing of CDH repair operation, complications and survival. There were 9 boys and 3 girls. All patients were prenatally diagnosed. Mean gestational age was 38.8± 1.7 weeks and mean birth weight was 3031 ± 499 gram. Mean age at the time of ECMO cannulation was 29.9± 28.9 hours. There were 4 patients who survived. Survivors showed higher 5 min Apgar scores (8.25 ± 0.96 vs. 7.00 ± 1.20, p=0.109), higher pre ECMO mean ph (7.258 ± 0.830 vs. 7.159 ± 0.986, p=0.073) and lower pre ECMO PaCO 2 (48.2± 7.9 vs. 64.8 ± 16.1, p=0.109) without statistical significance. The hernia was located on the left side in 10 patients and the right side in 2 patients. The time interval from ECMO placement to operative repair was about 3~4 days in 5 early cases and around 24 in the remaining cases. There were 3 cases of post operative bleeding requiring re operation and 2 cases of abdominal compartment syndrome requiring abdominal fascia reopening. ECMO catheter reposition was required in 4 cases. Three cases of arterial or venous thrombosis were detected and improved with follow up. Our data suggests that ECMO therapy could save the lives of some neonates with CDH who can not be maintained on other treatment modalities. Protocolized management and accumulation of case experience might be valuable in improving outcomes for neonates with CDH treated with ECMO. (J Kor Assoc Pediatr Surg 17(2):133~138), 2011. Index Words:Extracorporeal membrane oxygenation, Congenital diaphragmatic hernia Correspondence:Dae Yeon Kim, M.D., Asan Medical Center, Department of Pediatric Surgery, 86, Asanbyeongwon-gil, Songpa-gu, Seoul 138-736, Korea Tel : 02)3010-3961, Fax : 02-3010-6841 E-mail: kimdy@amc.seoul.kr