대한혈관외과학회지 : 제 24 권제 2 호 Vol. 24, No. 2, November, 2008 당뇨병성족부궤양의치료와절단에말초동맥질환이미치는영향 서울대학교의과대학 1 외과학교실, 2 내과학교실, 3 정형외과학교실, 4 성형외과학교실, 5 영상의학교실, 6 분당서울대학교병원당뇨족연구회 강미주 1 ㆍ최성희 2,6 ㆍ임수 2,6 ㆍ공현식 3,6 ㆍ박문석 3,6 ㆍ허찬영 4,6 ㆍ윤창진 5,6 ㆍ이태승 1,6 ㆍ김상준 1 The Impact of Peripheral Arterial Disease on the Treatment and Amputation of Diabetic Foot Ulcer Mee Joo Kang, M.D. 1, Seong Hee Choi, M.D. 2,6, Su Im, M.D. 2,6, Hyun Sik Kong, M.D. 3,6, Moon Seok Park, M.D. 3,6, Chan Yeong Heo, M.D. 4,6, Chang Jin Yoon, M.D. 5,6, Tae Seung Lee, M.D. 1,6 and Sang Joon Kim, M.D. 1 Departments of 1 Surgery, 2 Internal Medicine, 3 Orthopedic Surgery, 4 Plastic Surgery, 5 Radiology, Seoul National University College of Medicine, Seoul, 6 Seoul National University Bundang Hospital, Diabetic Foot Study Group, Seongnam, Korea Purpose: Diabetic foot ulcers are one of the most important complications of patients with diabetes for their quality of life. Yet the data on factors that affect the treatment outcome and the guidelines for a multidisciplinary approach are limited. The purpose of this study was to assess the clinical characteristics that affect healing of diabetic foot ulcers, and especially when this is associated with peripheral arterial disease (PAD). Method: We retrospectively reviewed the clinicopathologic data of 112 patients who were admitted for the treatment of diabetic foot ulcers from May 2004 to December 2007 at Bundang Seoul National University Hospital. The patient s demography and co-morbidities, the laboratory and radiological details, the surgical data and the treatment outcomes were evaluated and analyzed according to the presence of PAD. Result: The mean age of the patients was 66 years old and the male to female ratio was 2.3:1. Except for simple dressing of the ulcers, skin graft, amputation or revascularization were performed for 77 patients. Ulcers healed in 74 patients (66.1%) and recurrence was observed in 42 patients (37.5%). Major amputation was performed on 11 patients (9.8%). The non-healing group had a higher incidence of male gender (P=0.049), end stage renal disease (P=0.038), coronary arterial disease (P=0.018), the presence of PAD (P=0.034) and a higher level of cholesterol (P=0.011) and triglyceride (P=0.039). Patients with PAD had a lower ankle-brachial index (P<0.001) and a higher rate of undergoing revascularization (P<0.001), overall amputation (P=0.003), non-healing (P=0.034) and recurrence (P<0.001). After revascularization, the rate of major amputation was not reduced (P=0.915). Conclusion: The risk of non-healing, overall amputation and recurrence is increased in the presence of PAD. Evaluating the PAD status and multidisciplinary treatment strategies are needed to treat these patients with diabetic foot ulcer. Key Words: Diabetic foot, Ulcer, Peripheral arterial disease 중심단어 : 당뇨, 족부궤양, 말초동맥질환 서 론 책임저자 : 이태승, 경기도성남시분당구구미동 300 우 463-707, 분당서울대학교병원외과 Tel: 031-787-7092, Fax: 031-787-4055 E-mail: tslee@snubh.org 당뇨병의진단과치료의발전에따라당뇨병환자의생존기간이길어지면서삶의질에대한관심이높아지고있다. 당뇨병환자의 15 25% 는일생동안한번이상의족부궤양을경험하게되며 (1,2), 이로인한하지절단은일반인구의 10 30배에달한다 (3,4). 당뇨병성족부궤양은장기간 113
114 대한혈관외과학회지 : 제 24 권제 2 호 2008 에걸친집중적인치료를요하는질환으로환자및보호자의삶의질에영향을주고 (5) 의료비의상승을초래한다 (6). 당뇨병성족부궤양은여러가지동반질환을가진이질적인환자군에서발생한다. 말초동맥질환은족부궤양이있는환자의절반이상에서동반되어있고 (7) 당뇨병성족부궤양의중요한예측인자로주목받고있다 (8,9). 국내에서당뇨병성족부궤양의치료결과및예후에대한연구는많지않았고특히말초동맥질환의동반여부에초점을둔연구는없었다. 이에저자들은당뇨병성족부궤양의치료에영향을미치는요인을말초동맥질환의동반여부와관련하여분석하고자하였다. 또한당뇨병성족부궤양은여러진료과의유기적인협진을통한다각적접근을요하는질환이다. 현재까지당뇨병성족부궤양에대한치료는각진료과에서개별적으로행해졌으며이러한치료결과에대한연구는아직이루어지지않았다. 이에분당서울대학교병원에서는 2년전부터당뇨족연구회 ( 외과, 내과, 정형외과, 성형외과, 영상의학과 ) 를결성하여당뇨병성족부궤양의치료에관한일반적인합의점을도출하기위해노력해왔으며본연구를통해지금까지이루어진당뇨병성족부궤양에대한치료결과를분석함으로써향후당뇨병성족부궤양의표준진료지침확립의기초자료로사용할수있을것이다. 대상과방법 1) 대상 2004년 5월부터 2007년 12월까지분당서울대학교병원에서당뇨병성족부궤양으로진단받고입원치료한 112명의환자를대상으로하였다. 의무기록을통하여성별및연령, 당뇨병형, 당뇨병이환기간, 과거병력, 동반질환, 흡연유무, 인슐린치료유무, ankle-brachial index (ABI), 전산화단층촬영혹은혈관조영술소견, 공복시혈당, 혈중당화혈색소, 콜레스테롤, 지질검사결과, 수술소견과수술방법및치료결과를후향적으로분석하였고외래의무기록을기본으로추적조사를하였다. 2) 방법치료 6개월후족부궤양상태에따라치유군과비치유군으로나누어양군간임상지표를비교분석하였다. 최초치료이후완전히치유되었으나추적관찰기간중새로운병변이생긴경우및부분치유된후악화되어수술또는경피적혈관성형술등의추가적인치료가필요했던경우를재발로분류하였다. 재발이후치료방법을보존적치료, 수술, 경피적혈관성형술로나누어조사하였으며재발이후추가수술에는절개배농, 발가락이나전족부절단, 족관절이상의절단이포함되었다. 전체환자의추적관찰기간중재발이없었던환자 Table 1. Patient demographics Total (n=112) Healed (n=74) Unhealed (n=38) P-value Age (yr, mean±sd) 66.0±14.2 66.5±13.6 65.0±15.1 0.596 Sex (M:F) 2.3:1 1.74:1 4.4:1 0.049 Duration of Diabetes 19.2±10.4 19.6±10.0 18.4±11.1 0.596 Co-morbidity Hypertension 70 (63.6%) 48 (64.9%) 22 (66.1%) 0.701 ESRD 40 (36.4%) 22 (29.7%) 18 (50.0%) 0.038 Retinopathy 38 (34.2%) 24 (32.4%) 14 (37.8%) 0.572 Coronary artery disease 30 (27.3%) 15 (20.3%) 15 (41.7%) 0.018 CVA 22 (20.0%) 13 (17.6%) 9 (25.0%) 0.361 Smoking 24 (22.4%) 14 (19.2%) 10 (29.4%) 0.237 DM treatment Insulin 83 (74.1%) 54 (73.0%) 29 (76.3%) 0.360 Oral hypoglycemics 30 (26.8%) 23 (31.1%) 7 (18.4%) 0.201 Baseline ABI 0.81±0.36 0.81±0.38 0.81±0.34 0.979 Peripheral arterial disease 61 (54.5%) 35 (47.3%) 26 (68.4%) 0.034 Laboratory data FBS 254.3±165.2 235.6±158.1 290.4±174.5 0.097 HbA1c 8.4±1.9 8.2±1.8 8.7±2.0 0.187 Total cholesterol 183.6±49.4 174.9±40.6 200.0±60.0 0.011 Triglyceride 167.7±112.8 150.4±98.0 202.9±133.2 0.039 HDLC 44.7±13.5 45.6±14.2 42.9±11.9 0.403 LDLC 96.1±33.5 95.1±31.4 98.0±37.3 0.740
강미주외 : 당뇨병성족부궤양의치료와절단에말초동맥질환이미치는영향 115 를대상으로치유율을계산하였고재발율은전체환자중한번이라도재발이있었던모든경우를포함하였다. 말초동맥질환의진단은양측하지중어느한쪽이라도 ABI 0.9 이하인경우말초동맥질환이있는것으로판단하였고 ABI를시행하지않은환자들은임상소견을바탕으로전산화단층촬영이나혈관조영술소견상명백한다발성하지혈관의협착및동맥벽비후가있는경우말초동맥질환이있는것으로판단하였다. 이를바탕으로전체환자를말초동맥질환이환군과비이환군으로나누어임상양상을비교하였다. 하지절단은발가락이나전족부절단등보행에지장이없는경우를소절단 (minor amputation), 족관절이상의절단을대절단 (major amputation) 으로분류하였다. 외과적우회로술이나경피적혈관성형술을시행한경우에는혈관재개통이이루어진것으로보고혈관재개통군의임상경과를분석하였다. 3) 통계적분석 Windows SPSS 12.0 (SPSS Inc., Chicago, Il) 을이용하여임상지표들에대해 Student s t-test를사용하여평균비교를하였고 Chi-square test를사용하여교차분석을시행하였다. 궤양치유지연의위험인자분석을위해서는다중회귀분석을이용하였고각각의경우에있어서통계학적유의수준은 P값이 0.05 미만인경우로하였다. 결과 1) 연령, 성별분포및임상양상대상환자의평균연령은 66세로양군간차이가없었다. 2명의임신성당뇨환자를제외하고는모두제 2형당뇨병이었으며평균당뇨이환기간은 19.2년이었다. ABI는 64명 (57%) 의환자에서시행되었으며평균 0.81로양군간유의한차이는없었다. 비치유군은치유군에비해남자가많았고 (P=0.049), 만성신부전 (P=0.038) 및관상동맥질환 (P=0.018) 이동반된경우가많았다. 또한말초동맥질환의이환율이높았으며 (P=0.034) 혈중콜레스테롤 (P=0.011) 및지질 (P= 0.039) 수치가높았다 (Table 1). 이상의인자들을다중회귀분석하였을때유의한위험인자는성별 (P=0.022), 관상동맥질환 (P=0.036) 및만성신부전 (P=0.043) 의동반, 말초동맥질환유무 (P=0.049), 높은혈중콜레스테롤 (P=0.004) 및지질 (P=0.026) 수치였다. 2) 치료및결과수술적치료혹은경피적혈관성형술을시행한환자는모두 77명이었으며이중수술은 72명, 경피적혈관성형술은 22명에서시행되었다. 혈관우회술이시행된경우는 8명 (7.1%) 이었고대절단은 11명 (8.9%) 에서시행되었다. 최초치료후재발한환자는 42명 (37.5%) 이었고 28명 (25%) 에서추가수술이필요하였다. 치료 6개월후치유된환자는 74 명 (66.1%) 이었으며 10명 (8.9%) 의환자는궤양이치유되기전에사망하였다. 치료내용및결과를말초동맥질환이환여부에따라비교해보았을때, 말초동맥질환이있는경우 ABI 가낮았고 (P <0.001) 하지절단수술을시행하는경우가많았으나 (P= 0.003) 대절단비율은차이가없었다 (P=0.520). 또한치유율이낮았고 (P=0.034) 재발율이높았다 (P<0.001)(Table 2). Table 2. Interventions and outcome of DM foot ulcer Total Patients with PAD Patients without PAD (n=112) (n=61) (n=51) P-value Baseline ABI 0.81±0.36 0.65±0.30 1.13±0.24 <0.001 Operation 72 (64.3%) 49 (80.3%) 24 (47.1%) <0.001 Bypass 8 (7.1%) 8 (13.1%) 0 0.007 Amputation 48 (42.9%) 34 (55.7%) 14 (27.5%) 0.003 Minor 40 (35.7%) 30 (49.2%) 10 (19.6%) 0.006 Major 11 (9.8%) 7 (11.5%) 4 (7.8%) 0.520 Flap/Graft 8 (7.1%) 5 (8.6%) 3 (6.1%) 0.624 Debridement 23 (20.5%) 15 (24.6%) 8 (15.7%) 0.245 PTA 22 (19.6%) 21 (34.4%) 1 (2%) <0.001 Follow up (mo, median) 23.0 18.0 29.0 Outcome of foot ulcer Healed 74 (66.1%) 35 (57.4%) 39 (76.5%) 0.034 Under treatment 28 (25.0%) 19 (31.1%) 9 (17.6%) 0.100 Death before healing 10 (8.9%) 7 (11.8%) 3 (5.9%) 0.301 Recurrence 42 (37.5%) 32 (52.5%) 10 (19.6%) <0.001
116 대한혈관외과학회지 : 제 24 권제 2 호 2008 3) 혈관재개통 혈관재개통시술을시행한환자는모두 26명이었으며외과적우회로술이 8명, 경피적혈관성형술이 22명의환자에서시행되었다. ABI 및전산화단층촬영혈관조영결과말초동맥질환이환여부가명확하지않았으나궤양재발및창상치유지연으로경피적혈관성형술을시행한 1명을제외한 25명은모두말초동맥질환에이환되어있었다. 전체환자군중말초동맥질환에이환된환자는 61명이고, 그중혈관재개통시술을시행한환자 (n=25) 는그렇지않은환자에비해시술전 ABI가낮았으며시술전후 ABI는 0.56±0.31에서 0.95±0.37로증가하였으나통계적인유의성은없었다. 대절단비율및치유율은양군간차이가없었다. 혈관재개통군의시술이후대절단은 3예 (12%) 있었으며창상이치유된 20명의평균치료기간은 2.7개월이었다 (Table 3). 협착부위는장골동맥혹은대퇴동맥이하하지혈관의 Table 3. Outcomes of revascularization in patients with PAD Revascula- No revascularization rization P-value (n=25) (n=36) Baseline ABI 0.56±0.31 0.68±0.27 0.203 Post-procedural 0.95±0.37 0.319 ABI Amputation 15 (60.0%) 20 (55.6%) 0.383 Minor 12 (48.0%) 16 (44.4%) 0.784 Major 3 (12.0%) 4 (11.1%) 0.915 Outcome of foot ulcer Healed 20 (80.0%) 21 (58.3%) 0.076 Under treatment 4 (16.0%) 10 (27.8%) 0.282 Death before 1 (4.0%) 5 (13.9%) 0.202 healing Table 4. Summary of patients with PAD undergoing revascularization Level of arterial stenosis (n=25) Treatment Percutaneous Stent Bypass angioplasty insertion operation Diffuse Ilio-femoro- 4 4 2 0 tibial Focal Femoro-tibial 14 15 7 5 Ilio-femoral 2 1 1 1 Infra-popliteal 5 5 0 2 Multiple treatment strategies were used in each patients, including percutaneous angioplasty, stent insertion, or bypass operation 전반적인협착이있는경우가 18명으로가장많았고이들환자에서스텐트삽입 10예, 경피적혈관성형술 25예가시행되었으며스텐트삽입이나경피적혈관성형술없이외과적우회로술만시행한경우는 4예있었다 (Table 4). 고찰당뇨병성족부궤양은완치에서하지절단, 나아가사망에이르기까지다양한경과를보이는질환이다. 본연구에서는연구종료시점에서 66.1% 의환자가치유되었으며 8.9% 의환자는궤양이치유되기전에사망했고 9.8% 의환자에서슬관절하부절단이시행되었다. 이는 Jeffcoate 등 (10), Oyibo 등 (11) 의보고와유사한결과이며하지절단율은다소높은편이나보고된문헌마다절단범위의정의가명확하지않았기때문에본연구결과와단순비교할수는없다. 당뇨병성족부궤양이있는환자에서말초동맥질환의유병율은보고에따라 10 60% 에이른다 (8,11). 본연구에서말초동맥질환의유병율은 54.5% 였다. 말초동맥질환의정의와진단기준은일정하지않지만일반적으로휴식시 ABI 가 0.9 이하인경우말초동맥질환이있다고판단한다. 본연구에서는 ABI가시행된경우에는 ABI를기준으로, 시행되지않은경우에는임상소견을바탕으로전산화단층촬영이나혈관조영술소견상내강의 50% 이상협착이다발성으로존재하는지여부에따라말초동맥질환이환여부를판별하였다. 당뇨병성족부궤양은질병의특성상여러과에서다각적으로접근하게되어명확한치료지침이정해져있지않은경우일관된평가가어렵다는문제점이있다. 본연구에서는최초진료과에따라 ABI 시행비율이달랐는데전체환자중 57% 에서만 ABI 결과를수집할수있었으며혈관재개통이이루어진 26명의환자중시술이후의 ABI 추적이가능한경우는 58% 에불과하였다. ABI는비침습적이며쉽게결과를얻을수있고재현가능하며말초동맥질환진단에유용한검사방법이다 (12). 말초동맥질환에이환된환자중 1/3에서만하지파행이나타나고절반이상은무증상혹은비전형적인증상을보일뿐이나 (13) 말초동맥질환이있는환자에서심혈관계합병증의위험이높아져무증상의환자에서도정기적인 ABI 측정의중요성이강조되었다 (14). 그리고 Prompers 등 (9) 은당뇨병성족부궤양의독립적인위험인자로 ABI를기준으로한말초동맥질환을지목하였고 Nam 등 (15) 은 ABI 측정으로당뇨병성족부병변의치유가능성및예후를판단할수있다고하였다. 한편본연구에서는 ABI를측정한환자중 12.5% (n=8) 에서 ABI가 1.3 이상으로나타났다. 이처럼당뇨병환자에서는동맥벽의중막석회화로인한혈관탄성이줄어들어비정상적으로 ABI가높게나타날수있어이런경우발가락혈압을측정하여말초동맥질환이환여부를확인하는것
강미주외 : 당뇨병성족부궤양의치료와절단에말초동맥질환이미치는영향 117 이추천된다 (13). 본연구에서추적검사결과 ABI가높아진 3명을제외하고초기 ABI가 1.3 이상이었던환자 5명중 4 명은임상소견을바탕으로추가검사없이말초동맥질환비이환군으로분류하였으며, 나머지 1명에서발끝미세혈류검사를시행하였으며이환자는병행한전산화단층촬영결과말초동맥질환에이환된것으로판단되어경피적혈관성형술을시행하였다. 이상을종합할때체계적인환자관리및치료를위해어떤진료과를통해치료받게되더라도공통적으로적용할수있는진료지침의확립이요구되고이때 ABI 및필요한경우이중초음파, 발끝미세혈류검사, 경피적산소압측정, 전산화단층촬영및혈관조영술등을이용하여말초동맥질환이환여부를확인하는것이필요하겠다. 궤양자체의특성및감염여부를명확히규명하지못한점은본연구의가장큰한계점으로지적할수있겠다. 그러나기본임상지표및동반질환여부가궤양의치유지연에미치는영향을밝힐수있었다. 남자, 관상동맥질환및만성신부전이동반되어있는경우, 말초동맥질환에이환된경우, 혈중콜레스테롤및지질수치가높은경우궤양의치유가지연됨을알수있었다. Edward 등 (16) 은전향적연구에서부적절한혈당조절과인슐린치료가당뇨병성족부병변의위험을높인다고하였다. 본연구에서는비치유군에서공복혈당이다소높은경향을보였으나통계적으로유의하지않았고인슐린치료여부는치유및하지절단과유의한관계를보이지않았다. 혈관재개통을통해심각한하지허혈의개선및하지절단의위험을낮출수있다고알려져있다 (17). 실제로본연구에서혈관재개통술이후 ABI의현격한상승이관찰되어하지혈류공급의개선이이루어졌음을알수있었다. 경피적혈관성형술의성공률은협착부위의위치및길이에따라상이하지만 (18) 일반적으로 70 85% 의치료성공율및 5% 전후의하지절단율이보고되고있다 (17,19,20). 본연구에서는혈관재개통술로인한하지절단감소효과는명확히관찰되지않았다. 이는하지파행등의증상이있고혈관조영술상 50% 이상의협착이있는경우우선적으로경피적혈관성형술을시행한외국의보고들 (17,18) 에비해궤양이발생한후경골및비골동맥모두협착이있는것이확인되어차선의방법으로경피적혈관성형술을시행한경우가 73% 에달하는대상환자군의특성에기인한차이로생각할수있다. 또한대절단이시행된 3예 (12.0%) 는환자가수술을거부하여적절한치료시기를놓쳤거나경피적혈관성형술후잔여유착이 50% 이상으로시술후적절한원위부혈류공급이회복되지않은경우였다. 말초동맥질환에이환된환자중혈관재개통술을시행한경우 80% 의환자에서궤양또는창상이치유되어통계적으로유의하지는않았지만혈관재개통술을시행하지않은경우보다치유율이높은경향을보였다 (P=0.076). 또한피 판형성술혹은하지절단이후보조적으로경피적혈관성형술이시행된 3예에서는혈관재개통이후창상치유의개선을확인할수있었다. 그러나혈관재개통술이후 76% 의환자에서임상적재발이관찰되었으며전체환자군에서혈관재개통술여부에따른치유율의차이가없었던본연구의결과와연관지어생각해볼때, 이는혈관재개통술이일시적으로는하지혈류의개선을가져왔지만당뇨환자에서의미세혈관합병증이근본적으로해결되지않았기때문이었으리라생각된다. 결 당뇨병성족부궤양은환자의삶의질에큰영향을미치며적절한치료가이루어지지않았을경우하지절단, 사망에이를수있는질환이다. 신부전, 관상동맥질환등의대혈관합병증과더불어말초동맥질환이동반된경우하지절단확률이높아지고치유지연및재발의위험이높아지므로 ABI 측정등을통한환자선별및조기발견이필요하다. 혈관재개통술은하지혈류개선에도움을주었고하지절단감소효과의확인을위해확대된적응증및다수의환자를대상으로한추가적인연구가필요하겠다. 론 참고문헌 1) Reiber GE. The epidemiology of diabetic foot problems. Diabet Med 1996;13(suppl 1):S6-S11. 2) Lavery LA, Armstrong DG, Wunderlich RP, Tredwell J, Boulton AJ. Diabetic foot syndrome: evaluating the prevalence and incidence of foot pathology in Mexican Americans and non-hispanic whites from a diabetes disease management cohort. Diabetes Care 2003;26:1435-1438. 3) Siitonen OI, Niskanen LK, Laakso M, Siitonen JT, Pyorala K. Lower-extremity amputations in diabetic and nondiabetic patients: a population-based study in eastern Finland. Diabetes Care 1993;16:16-20. 4) Trautner C, Haastert B, Giani G, Berger M. Incidence of lower limb amputations and diabetes. Diabetes Care 1996;19: 1006-1009. 5) Nabuurs-Franssen MH, Huijberts MS, Nieuwenhuijzen Kruseman AC, Willems J, Schaper NC. Health-related quality of life of diabetic foot ulcer patients and their caregivers. Diabetologia 2005;48:1906-1910. 6) Apelqvist J, Ragnarson-Tennvall G, Persson U, Larsson J. Diabetic foot ulcers in a multidisciplinary setting. An economic analysis of primary healing and healing with amputation. J Intern Med 1994;235:463-471. 7) Prompers L, Huijberts M, Apelqvist J. High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline resultsfrom the
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