부산대병원학술지통권제 35 호, 2014 혈액투석환자에서동정맥루폐색의조기진단 부산대학교의과대학내과학교실 이동원, 김일영, 이수봉 Early detection of vascular access stenosis in hemodialysis patients Dong Won Lee, Il Young Kim, Soo Bong Lee Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea Abstract* The long-term survival and quality of life of patients on hemodialysis (HD) are dependent on the adequacy of dialysis via an appropriately placed vascular access. The optimal vascular access is unquestionably the autologous arteriovenous fistula (AVF), with the most common method being the conventional radio-cephalic fistula at the wrist. Recent clinical practice guidelines recommend the creation of native fistula or synthetic graft before the start of chronic HD therapy to prevent the need for complication-prone dialysis catheters. This could also have a beneficial effect on the rapidity of worsening kidney failure. A multidisciplinary approach - nephrologists, surgeons, radiologists and nurses - should improve the HD outcome by promoting * 본연구는 2012년도양산부산대학교병원임상연구비지원으로이루어졌음. - 33 -
이동원, 김일영, 이수봉 the use of AVF. An important additional component of this program is the Doppler ultrasound for preoperative vascular mapping. Such an approach may be realized without unsuccessful surgical explorations, with a minimal early failure rate and a high maturation, even in patients with diabetes mellitus. The most important thing is to detect the development and progression of stenosis in time to prevent any eventual thrombosis. The final trigger causing thrombosis is the critical reduction of arterial blood flow below 200 ml/min. So continuous close monitoring and surveillance are essential for long-term survival of the vascular access. Key Words : Hemodialysis, Arteriovenous fistula, Thrombosis, Diagnosis 서론 혈액투석을받고있는만성신부전환자에있어서적절한동정맥루의확보와유지는성공적인투석의필수요소일뿐아니라환자의유병률과사망률에영향을미치는주된요인이다. 이상적인혈관통로는투석처방에따라적절한혈류속도를유지할수있어야하고, 장기간사용할수있어야하며감염, 혈전, 협착, 가성동맥류및사지허혈과같은합병증발생이적어야한다. 그러나만성신부전환자의입원원인중가장흔한것은동정맥루와관련된질환이며 (USRDS, US renal data system, 2001), 정맥협착과관련된정맥혈전증에의한동정맥루폐쇄가가장큰원인으로알려져있다. 또한정맥협착증은자가혈관에비해인조혈관에서많이발생하며인조혈관-정맥문합부혹은동맥-정맥문합부에서주로발생한다. 따라서미국신장재단 (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative, NKF-K/DOQI) 의지침 에서는이러한합병증을줄이고혈액투석환자의삶의질과예후를향상시키기위해환자자신의혈관을이용한동정맥루수술빈도를증가시키고동정맥루폐쇄가발생하기전에동정맥루기능이상을조기에발견하도록권고하고있다. 혈관통로조성술의역사 지속적인유지혈액투석요법을받고있는만성신부전환자에서는혈관통로의확보가장기적인투석유지에필수적인요소이다. 1960년에 Quinton, Scribner 등에의해처음시도된외부형동정맥루는 Teflon tube를요골동맥과인접정맥에각각루프형식으로접합하여손목외부에노출시킨방식으로서장기간사용할수있는혈관통로로널리사용되었으나반복적인혈전형성과감염등으로인해사용에제한이있었다. 이에따라 1966 년 Cimino, Brescia 등은피하의요골동맥 (radial artery) 과두정맥 (cephalic vein) 을 - 34 -
혈액투석환자에서동정맥루폐색의조기진단 연결하여내부형동정맥루를개발함으로써현재까지가장널리사용되고있다. 이후 1976 년 PTFE 인조혈관이개발되어자가혈관시술이어려운환자에서유용한대안으로널리사용되고있으며 1979년내격정맥, 쇄골하정맥등에시술가능한혈관카테터가개발되어일시적인혈액투석에활용되고있으며 1988년에는피하매복형혈관카테터가개발되어사용되고있다. 또한 2000년에는피하매복형혈액투석포트가개발됨으로써동정맥루및카테터사용과관련된혈관합병증들을감소시킬수있는대안으로제시되고있다. 혈관통로조성술의특성 자가혈관을이용한동정맥루는현재까지사용되는혈관통로중에서이상적인조건에가장근접한방법으로서가장우수한장기개존률 (primary patency rate) 을보이고있으며중재적시술의필요성도가장낮은결과를보이고있다. K/DOQI 지침에서는주로사용하지않는팔 (non-dominant arm) 손목의요골동맥-두정맥문합술 (radial-cephalic fistula) 이첫번째추천되고이후상완동맥-두정맥문합 (brachial-cephalic fistula), 상완동맥-척측피정맥전위문합 (brachial-basilic transposition fistula) 등의순서로추천되고있다 ( 그림 1). 표 1. 이상적인혈관통로의조건 Easy repetitive access to the circulation A b ility to re lia b ly p ro v id e 4 0 0 m L /m in b lo o d flo w Blood flow at the end of dialysis can be term inated easily and quickly F u n c tio n fo r th e life o f th e p a tie n t F re e d o m fro m c o m p lic a tio n Cosm etically acceptable 1 그림 1. 자가혈관을이용한동정맥루시술의종류 (From Kidney Int 2002;62:1109-1124) - 35 -
이동원, 김일영, 이수봉 자가혈관동정맥루는인조혈관에비해서비교적안전하고용이하게조성이가능하지만사용까지혈관성숙기간 ( 약 3-4개월추천 ) 이필요한제한점이있고시간이지남에따라혈관의크기와혈류량이증가하게되어혈류량확보에잇점이있는반면외관상의문제점및심혈관에대한부담증가등이단점으로지적되고있다. 그러나인조혈관에비해서정맥혈전증과감염등의합병증발생이적어오랜기간혈관통로를유지할수있는장점이있다 ( 표 2). 표 2. 각혈관통로의장, 단점 ( 이상적인조건에대한만족도 ) 표 3. 조기동정맥루기능부전의원인후기동정맥루기능부전은사용 3개월이후에발생하는혈관통로부전증으로정의하며가장흔한원인은정맥협착증으로전체협착증의 80% 가정맥협착증에의해발생한다. 나머지 20% 는뚜렷한혈관병변없이나타날수있는데투석후지혈목적의과도한압박, 투석시주사기전차의기술적결함, 저혈압, 체액량부족, 수면중동정맥루압박및동맥협착증등이원인이다 ( 표 4). 표 4. 후기동정맥루기능부전의원인 AVF, arteriovenous fistula; AVG, arteriovenous graft 정맥혈전증의원인 조기동정맥루기능부전은동정맥루시술후사용하기전또는사용후 3개월이내에발생하는혈관통로부전증으로정의한다. 조기부전의원인은유입장애 (inflow problems) 와유출장애 (outflow problems) 로구분하며대부분은혈관통로시술전충분한혈관상태파악을통해서미연에방지될수있는것들이다 ( 표 3). 정맥협착증의발생기전 정맥협착증은자가혈관에비해인조혈관에서잘발생하며인조혈관-정맥문합부혹은동맥 -정맥문합부에근접한정맥에서가장많이발생한다. 그외에문합부, 근위부정맥과쇄골하정맥혹은무명정맥등의중심정맥부위및문합부에근접한동맥부위에서도발생한다. - 36 -
혈액투석환자에서동정맥루폐색의조기진단 정맥협착증은혈관내막증식과반복적인주사기천자에의한혈관내막의손상, 동정맥루조성후발생하는과도한혈류등에의해서발생한다. 혈관벽이손상되면여러성장인자, 즉 PDGF, TGF-β, EGF 등이관여하여평활근세포와섬유아세포등을활성화시켜내막을증식시킨다. 정맥협착증은동정맥루사용전에도발생할수있는것으로, 전체동정맥루의 20-25% 정도는혈액투석에사용될수있을정도로정맥이자라지않는것으로보고되고있다. 또한불충분한정맥성숙으로혈액투석이불가능하였던환자들의 39% 에서정맥협착증이발견되었던보고도있었다. 이러한동정맥루사용전발생하는정맥협착증의발생기전은현재까지정확하게알려져있지않으나동정맥루수술시정맥의과도한당김및비틀림등에의한손상이관여할것으로생각된다. 쇄골하정맥등의중심정맥협착증은주로과거도관삽입과관련이있는데쇄골하정맥도관삽입의 50% 에서협착증이발생되는것으로보고되고있으므로가능한한쇄골하정맥도관삽입은피할것을권고하고있다. 도관삽입의기간이길거나획수가많거나도관감염이발생하게되면협착증이발생할위험성이커지게된다. 정맥협착증의진단방법 표 5. 정맥협착증의진단 1. Monitoring 동정맥루정맥협착증은대부분서서히진행되므로초기에는별다른증세가나타나지않고혈관내경 70% 이상의협착이진행되면증세가나타나기시작한다. 따라서지속적인진찰을통해다음과같은소견이관찰될경우조기에치료적개입이필요하다 ( 표 6). 표 6. 정맥협착증의임상증상및진찰소견 - 37 -
이동원, 김일영, 이수봉 2. Surveillance 1) 동정맥루혈류 (Intra-access blood flow) 혈액투석에적절한동정맥루는동정맥루내의혈류가최소투석기계의혈류속도보다높아야한다. 동정맥루의혈류가낮으면투석의적절도가떨어지며시간이경과되면서동정맥루가폐쇄되기쉽다. 그러므로정기적으로동정맥루의혈류를측정하면동정맥루의폐쇄를조기에예방할수있다. 도플러초음파에의한혈류측정은인조혈관에서는매우유용하지만자가혈관에서는정맥협착증이발생되더라도부수정맥 (collateral vein) 이형성됨으로써혈류가협착정도에비례하여감소되지않기때문에민감도가낮은것으로알려져있다. 미국신장재단에서는투석시작후 1.5시간이내에초음파희석법 (ultrasound dilution), 전도희석법 (conduction dilution), 열희석법 (thermal dilution) 및도플러초음파로매달혈류를측정하여혈류속도가 600 ml/min 이하이거나 4개월간에 25% 이상감소한혈류속도가 1000 ml/min 이하일경우에는동정맥루조영술을시행하도록권고하고있다. 이러한혈류속도의측정은동정맥루협착의예측인자일뿐아니라협착에대한침습적치료의성공여부를결정하는데중요한지표가된다. 표 7. 동정맥루혈류를측정하는 transonic technique 1. Reverse the blood lines. 2. Attach the ultrasonic probes to the blood lines. 3. Adjust flow to 300 ml/min; be sure that ultrafiltration is turned off. 4. Set transonic device for blood flow measurement. 5. Administer of bolus of saline when directed by the message on the computer screen. 6. Record the value given on the computer screen. 7. Do test three times and take the average. 1 2) 동적정맥압 (Dynamic venous pressure) 투석중동적정맥압은투석기를통해자동으로측정되기때문에비교적간편하게측정할수있는정맥압으로일정한혈류속도에서투석시작 5분이내에측정하는데정맥압이증가할경우동정맥루상부의정맥협착증을암시한다. 그러나투석용주사기의바늘구경및위치, 혈류속도, 혈액점도등의영향을받을수있으므로바늘끝이혈관벽에닿지않도록하고혈류속도와혈액점도가일정한투석초기에시행하는것이바람직하다. 3회연속측정하여정맥압이임계치 (125~150 mmhg) 이상증가되어있는경우정맥협착증을의심해야한다. 표 8. 동적정맥압측정법 For all patients - Measure venous pressure from the HD machine at Qb 200 ml/min during the first 2-5 min of HD at every session - Use 15G needles - Assess at the same time level relative to HD machine for all measurements - Look for persistence and trend over time For new patients - Establish a baseline by initiating measurements when the accessis first used - Pressure must exceed the threshold 3 times in succession to be significant For established patients - Pressure must exceed 120 mm 3 times in succession to be significant 1 3) 정적정맥압 (Static venous pressure) 투석중정적정맥압은혈류속도 0인상태에서측정하는정맥압으로, 동적정맥압에비해주사기구경및위치, 혈류속도, 혈액점도등의변수에영향을받지않기때문에정확도가높다. 그러나특정한보조장치가측정에필요하기때문에임상적용에제한이되고있다. 미국신장재단에서는정맥협착증의진단방법으로동정맥루혈류측정과정적정맥압측정방법을권장하고있다. - 38 -
혈액투석환자에서동정맥루폐색의조기진단 4) 요소재순환율 (Urea recirculation ratio) 요소재순환은혈액투석시투석이이루어진혈액이다시동맥도관을통해투석에유입되는비율을일컬으며동맥혈의혈류가적거나정맥협착증등으로정맥압이증가된경우에높게나타난다. 말초혈액의채취방법에따라 three-needle method와 two-needle method로나뉘는데 three-needle method의경우말초정맥에서혈액을채취해야하고동정맥루재순환이외에심폐재순환의영향을받기때문에최근에는 two-needle method가권장되고있다. 요소재순환율이 10% 이상이면정맥협착을의심할수있고, 요소재순환율의변화는동정맥루협착의후기예측인자역할을하는것으로알려져있다. 그러나혈류속도, 심부전유무, 주사기구경및주사부위간간격등의영향을받을수있기때문에단독으로적용하기보다는정맥압등의다른방법과함께사용하는것이유리하다. 5) 투석적절도 (Adequacy of hemodialysis delivery) 정기적인투석적절도의검사도정맥협착증의진단에도움이된다. 특별한이유없이 Kt/V, Urea reduction ratio(urr) 등이감소하는경우정맥협착증을의심해볼수있다. 그러나이러한투석적절도측정치는정맥협착증외에다른인자들에의해영향을받을수있기때문에민감도와특이도가낮아다른검사방법들과함께사용하는것이바람직하다. 6) 동정맥루조영술 (Fistulography) 동정맥루조영술은정맥협착증의확진에필요한검사법이다. 동정맥문합부에근접한정 맥을천자한후조영제를주사하여말단정맥에서부터중심정맥까지의상태를확인하고, 천자부위상단을압박한후조영제를주사하여동정맥문합부와이에인접한동맥의상태를확인한다. 여러가지검사에서정맥협착이의심되면반드시동정맥루조영술을시행하여협착의위치와정도를파악함으로써적절한치료방법을선택할수있도록해야한다. 표 9. 요소재순환율측정법 Perform test after approx. 30 min of treatment and turning off ultrafiltration 1. Draw arterial (A) and venous (V) samples. 2. Immediately reduce blood flow rate (BFR) to 120 ml/min. 3. Turn blood pump off exactly 10 seconds after reducing BFR. 4. Clamp arterial line immediately above sampling port. 5. Draw systemic arterial sample (S) from arterial line port. 6. Unclamp line and resume dialysis. 7. Measure BUN in A, V and S samples and calculate % recirculation (R). 1 R = ( S-A / S-V ) x 100 결론 혈액투석환자에서동정맥루폐쇄의가장흔한원인인정맥협착증의조기진단과예방은혈액투석환자의이환율을감소시키고치료비용을절감할뿐아니라삶의질향상에도움이된다. 따라서동정맥루유지및감시에모든의료진들의노력이집중되어야하며정기적인검사를통해이상소견이발견되면적극적인치료노력을게을리해서는안된다. 그리고의료진뿐아니라환자및보호자들을대상으로동정맥루관리및응급조치에대한지속적인교육이필요하다. 또한혈관자체의병변뿐아니라고령, 고혈당, 투석중저혈압등동정맥루폐쇄가호발하는고위험군들에대한전반적인관리가필요할것으로생각된다. - 39 -
이동원, 김일영, 이수봉 표 10. 기본적인환자교육항목 All patients should be taught how to 1. Compress a bleeding access 2. Seal the site of a central venous catheter with ointment to keep air embolus from entering 3. Wash skin over access with soap and water daily and before dialysis 4. Recognize signs and symptoms of infection 5. Select proper methods for exercising AV fistula arm with some resistance to venous flow 6. Palpate for thrill/pulse daily and after any episodes of hypotension, dizziness, or lightheadedness 7. Listen for bruit with ear opposite access if cannot palpate for any reason All patients should know to 1. Avoid carrying heavy items draped over access arm or wearing occlusive clothing 2. Avoid sleeping on the access arm 3. Insist that staff rotate cannulation sites daily 4. Insure that staff are using proper techniques in preparing skin prior to cannulation 5. Report any signs and symptoms of infection or absence of bruit/thrill to dialysis 1 personnel immediately 참고문헌 1. Murray JE, Merrill JP, Harrison H. Kidney transplantation between seven pairs of identical twins. Ann Surg 1958;148:343-59. 2. 김유선, 김명수, 김순일등. 사이클로스포린을투여한일차생체신이식의생존율과예후인자의분석. 대한신장학회지 1996;15: 184-93. 3. 김남호, 이성철, 김수완등. 신장이식 100예의임상적고찰. 대한신장학회지 1995;14:388-98. 4. 곽재용, 박성광, 강성귀. 신장이식환자의임상적분석. 대한내과학회지 1994;47:792-802. 5. 윤영석, 김용수, 방병기등. Catholic Medical Center 에서의신이식 22년-생체신이식 600예의결과. 대한내과학회지 1992;43:473-86. 6. Terasaki PI, Cecka JM, Cho Y. Overview, in Clinical transplants 1990. Los Angeles, UCLA Tissue Typing Laboratory, 1990;585-90. 7. Hunsicker LG, Held PJ. The role of HLA matching for cadaveric renal transplants in the cyclosporine era. Seminars in Nephrol 1992;12:293-303. 8. Steve Takemoto BS, Terasaki PI, Cecka JM, Cho YW, Gjertson DW. Survival of nationally shared, HLA-matched kidney transplants from cadaveric donor. New Engl J Med 1992;327:834-9. 9. 김용신, 정구용, 김유선등. 50세이상의고령환자에서시행된신장이식의결과. 대한이식학회 1992;6:47-53. 10. Andreu J, de la Tore M, Oppenheimer F, Campistol JM, Richard MJ, Vilaedel J, et al. Renal transplantation in elderly redipients. Transplant Proc 1992;24 :120-1. 11. Riera L, Seron D, Castelae AM, Grino JM, Franco E, Bover J, et al. Renal transplantation in cyclosporine-treated patients over age 50. Transplant Proc 1992;24:122-3. 12. Matas AJ, Gillingham KJ, Sutherland DER. Half-life and risk factors for kidney transplant outcome-importance of death with function. Transplantation 1993;55:757-63. 13. Cecka JM, Cho YW, Terasaki PI. Analysis of the UNOS scientific renal transplant registry at three year-early events affecting transplant success. Transplantation 1992;53: 59-64. 14. 김지훈, 이준승, 장상필등. 서울중앙병원신장이식의임상적분석. 대한신장학회지 1999;18:974-83. 15. Zhou YC, Cecka JM. Effect of HLA matching on renal transplant survival, in Clinical Transplants 1993, Los Angeles, UCLA Tissue Typing Laboratory, 1994;499-510. 16. Cho YW, Cecka JM, Terasaki PI. HLA matching effects: Better survival rates and graft quality, in Clinical Transplants - 40 -
혈액투석환자에서동정맥루폐색의조기진단 1994, Los Angeles, UCLA Tissue Typing Laboratory, 1995;435-49. 17. Mendez R, Cicciarelli J, Mendez RG et al. HLA matching at a single kidney transplant center. Transplantation 1991;51:348-50. 18. Yoon YS, Jin DC, Yang CW et al. The effect of HLA mismatching on graft survival in living-donor kidney transplants. Catholic Medical Center, 1984 to 1993, in Clinical Transplants 1993, Los Angeles, UCLA Tissue Typing Laboratory, 1994;275-83. - 41 -