대한골절학회지제 17 권, 제 4 호, 2004 년 10 월 Journal of the Korean Fracture Society Vol. 17, No. 4, October, 2004 항생제혼합시멘트정을이용한장관골감염성불유합의이단계치료 조세현 정순택 박형빈 황선철 하용찬 황인환 경상대학교의과대학정형외과학교실 목적 : 장관골감염성불유합의치료시항생제혼합시멘트정을이용한이단계재건술의결과를분석하고자한다. 대상및방법 : 1998 년 1월부터 2002 년 9월까지장관골감염성불유합으로이단계재건수술을받은 41예 ( 대퇴골 26예, 경골 15예 ) 를대상으로하였다. 일단계수술에서는광범위한변연절제술, 부골제거및세척술과기존고정장치의제거또는외고정장치로의교환을시행한후사공 (dead space) 과불유합주변연부조직내항생제혼합시멘트정을삽입하였다. 임상적감염증상이호전된평균 8.7주 (3주 ~32주 ) 후이단계재건술로서 I군은내고정장치 ( 금속판 5예, 골수강내금속정 8예 ), II군은외고정장치 (Ilizarov 25예, Monofixator 3예 ) 로각각고정하고 17예에서는골내이동술이나골연장술을시행하였다. 양군모두필요한경우골이식과시멘트정의교환을추가하였다. 추시기간은 16개월에서최장 71개월로평균 45개월이었다. 치료결과는골유합기간및 Paley 방법에의한방사선상골유합상태와하지기능으로평가하였다. 결과 : I군 13예전부와 II군 28예중 26예에서감염의치료와골유합을얻었다. 이단계재건술후골이식술, 골소파술, 외고정핀교환과각변형교정술, 피부이식또는근육피판회전술등의보조적시술이 I군은평균 2회, II군은평균 6.2회추가되었다. 평균골유합기간은 I군이 19.3 주이고 II군이 23.1 주로내고정군이더빨랐다. 방사선상 Paley 골유합상태는 I군이우수 8예, 양호 5예이었고, II군이우수 18예, 양호 7예, 보통 1예, 불량 2예이었다 (p=0.492). 기능적결과는 I군에서우수 6예, 양호 6예, 보통 1예이었고, II군에서는우수 10예, 양호 13 예, 보통 3예, 불량 2예이었다 (p=0.267). 결론 : 항생제혼합시멘트정의골수염치료효과가관찰되었으며, 감염이호전된후내고정장치로교환해준군이외고정을유지한군에비하여추가수술횟수가적고, 골유합기간도빨랐다. 색인단어 : 장관골, 감염성불유합, 항생제혼합시멘트정, 내고정술, 외고정술, 이단계치료 Two-Stage Reconstruction of Infected Nonunion of Long Bones using Antibiotics-Impregnated Cement Beads Se-Hyun Cho, M.D., Soon-Taek Jeong, M.D., Hyung-Bin Park, M.D., Sun-Chul Hwang, M.D., Yong-Chan Ha, M.D., In-Hwan Hwang, M.D. Department of Orthopaedic Surgery, College of Medicine, Gyeong-Sang National University Jinju, Korea Purpose: To evaluate treatment results between internal and external fixation groups in two-stage reconstruction of infected nonunion of long bones using antibiotics-impregnated cement beads. Materials and Methods: In the first stage, preexisting hardwares were removed and radical debridement was done. The dead space was filled with antibiotics -impregnated cement beads and the nonunion site was immobilized by external fixation, cast or skeletal traction. In the second stage, all cases were divided into two groups; the nonunion was fixed by internal fixation in group I versus external fixation in group II. The intervening period between the first and second stage was average 8.7 weeks (range, 3~23 weeks). Results: The follow-up period was average 45 months (range, 16~71 months). Infection control and bone union were achieved in all 13 cases of group I. Infection recurred in two of 28 cases in group II, one underwent above-knee amputation and the other case was lost in follow-up. The mean number of supportive operations including repeated curettage, augmentation and change of infected pins, angular correction, and soft tissue flap was average 2 and 6.2 times respectively in group I and group II. Bony union period was average 19.3 and 23.1 weeks in each group. According to Paley's classification, group I was similar to group II in bony and functional result (p>0.05). Conclusion: Antibiotics-impregnated cement beads provided positive effect on infection control. Internal fixation group showed less number of additional operations and earlier bony union than external fixation group. Key Words: Long bone, Infected nonunion, Antibiotics-impregnated cement beads, Internal fixation, External fixation, Two-stage reconstruction 통신저자 : 조세현경상남도진주시칠암동 90 번지경상대학교의과대학정형외과 Tel : 82-55-750-8100 Fax : 82-55-755-8365 E-mail : shcho@nongae.gsnu.ac.kr Address reprint requests to : Se-Hyun Cho, M.D. Department of Orthopaedic Surgery, College of Medicine, Gyeong-Sang National University, 90 Chilam-dong, Jinju, 660-751, SOUTH KOREA. Tel : 82-55-750-8100 Fax : 82-55-755-8365 E-mail : shcho@nongae.gsnu.ac.kr 395
396 조세현, 정순택, 박형빈, 황선철, 하용찬, 황인환 서론장관골감염성불유합은재발과합병증이빈번하고, 시간과비용이많이소모되는치료가어려운질환이다. 치료방법의선택과예후는불유합의위치, 연부조직및골의감염정도, 세균의동정과민감한항생제의선택여부, 고정의안정성등다양한요소에의해결정된다 11). 일반적으로변연부절제술과전신적항생제투여가치료의근간을이루고있으며, 골결손부는해면골이식술, 혈관부착골이식술과골신연술등으로재건시키고있다 5,19,20,21). 저자는항생제혼합시멘트정을이용한이단계재건술의결과를분석하여장관골감염성불유합의치료경험을문헌고찰과함께보고하는바이다. 대상및방법 1998년 1월부터 2002년 9월까지본원에서장관골감염성불유합으로진단된후항생제혼합시멘트정을이용한이단계재건수술을받은 41명 41예 ( 대퇴골 26예, 경골 15예 ) 를대상으로하였다. 연구대상인양군 ( 내고정 I군과외고정 II 군 ) 은 Table 1에서명시한바와같이초기골절양상에따른 Gustilo와 Anderson 6) 의분류에따라짝짓기를하였고, 짝짓기한양군간에방사선학적으로술전골결손의차이는 1 cm 미만, 이학적으로감염부위국소적소견의호전과염증수치 (CRP 10 이하, ESR 25 이하 ) 가비슷한것을기준으로나누었다 (Table 1). 남자가 33명, 여자가 8명이었고연령은 17세에서 82세로평균 44세 ( 남자가 17세에서 62세로평균 39.6 세, 여자가 47에서 82세로평균 59.8세 ) 였다. 수상원인은교통사고가 26예 ( 운전자교통사고 14예, 보행자교통사고 4예, 오토바이사고 8예 ), 낙상에의한경우가 10예, 경운기전복이 3예, 벨트손상이 2예였다. 최초골절양상은개방성골절이 26예 (Gustilo & Anderson 제1형 7례, 제2형 5례, 제3형- A 4례, 제3형-B 5례, 제3형-C 5례 ) 였고나머지 15예는폐쇄성골절 ( 수술후감염발생 ) 이었다. 최초골절의고정은 17 예 (41%) 에서내고정 ( 금속판 10예, 골수강내금속정 7예 ) 으로, 24예 (59%) 에서외고정 (Ilizarov 고정 18예, Monofixator 고정 6예 ) 으로고정하였다. 평균수상일로부터감염발생으로인하여본원에서치료를받기까지의기간은평균 11개월로최단 5개월에서최장 48개월까지였다. 본원에내원하기까지타병원에서 1회내지 14회의수술적치료를시행받았으며평균 4.8회였다. 수술전에골결손의정도, 감염균주의동정, 연부조직의상태및인접관절의상태등을분석하였다. 치료전균주및항생제내성검사에서 31예의황색포도상구균 (Methicillin-resistant Staphylococcus aureus) 은 Van- comycin, 5예의녹농균 (Pseudomonas aeruginosa) 은 Gentamicin, 2예의그람음성균 (Enterobacter aerogenes와 Enterobacter cloacae) 은 Cephalosporin에민감하였으며, 나머지 3예는균주검사에서음성이었다. 이들세항생제는시멘트의 polymerization시발생되는열에도그효과가크게감소되지않는것으로알려져있다 8,10,13). 일단계수술에서는광범위한변연절제술, 부골제거및세척술과기존내고정장치의제거, 석고고정, 골견인또는다른외고정장치로의교환을시행한후사공 (dead space) 과불유합주변연부조직내항생제혼합시멘트정을삽입하였다. 삽입된항생제혼합시멘트정은 vancomycin 1 gm, 3세대 cephalosporin인 cefotaxime 1 gm과 gentamicin 5 mg 세가지항생제를분말상태에서골시멘트 (Osteobond; Zimmer, Warsaw, IN, USA) polymer 40 gm와균질하게섞은후액체시멘트 (methylmethacrylate monomer) 20 cc를혼합하여제조하였다. 항생제정맥투여는평균 2주간투여하였으며, 모든환자에서제2세대 Cephalosporin을하루 1 gm씩 2회그리고 Aminoglycoside계 (Netilmicin) 를하루 150 mg씩 2회투여하였고, 균동정이이루어진경우는민감한항생제로전환하여선택적으로투여하였다. 감염부위의국소적소견과임상혈액학적소견인 C-반응성단백수치및적혈구침강속도가호전된평균 8.7주 (3주 ~32주 ) 후시행된이단계재건술로서 I군은내고정장치 ( 금속판 5예, 골수강내금속정 8예 ), II군은외고정장치 (Ilizarov 25예, Monofixator 3예 ) 로각각고정하고 17예에서는골내이동술이나골연장술을시행하였다. 양군모두필요한경우골이식과시멘트정의교환을추가하였다. 골이식술은이전수술에서의골이식여부및일차수술시측정된골결손의정도에따라결정하였으며, 자가해면골이식을원칙으로하여동종골을추가하였다. 관절운동은환자의통증양상과임상적고정에따라이단계재건술후 I군은 5~ 7일째실시했고, II군은 1~2주째실시했다. 추시기간은 16 개월에서최장 71개월로평균 45개월이었다. 치료결과는골유합기간및 Paley 4,15) 에의한골유합상태 ( 골유합, 감염유무, 변형과하지부동유무에따라우수는골유합을얻고감염소실, 7도이내의변형, 2.5 cm 이하의하지부동이있는경우, 양호는골유합을얻고나머지기준에서두가지를포함할경우, 보통은골유합을얻고나머지한가지기준을만족할경우, 불량은골유합을얻지못한경우 ) 와하지기능 ( 동통, 관절구축, 연부조직위축, 보행시파행의유무및일상생활수행능력정도에따라우수는환자가어려움없이일상생활을수행하며파행, 관절구축, 연부조직위축, 동통이없을때, 양호는어려움없이일상생활을수행하지만다른기준중한가지또는두가지가있을때, 보통은일상생활을어려움없이수행하지만네가지전부가있거나절단을하였을경우, 불량은일상생활에심각한장애가있는경
항생제혼합시멘트정을이용한장관골감염성불유합의이단계치료 397
398 조세현, 정순택, 박형빈, 황선철, 하용찬, 황인환 A B C D Fig. 1. A 55-year-old female had undertaken IM nailing for closed fracture of femoral midshaft after fall down accident, which resulted in nonunion and chronic osteomyelitis with draing sinus. (A) Radiographs on referral: External fixation was done at the primary hospital, but developed active draining infective nonunion. (B) Complete debridement and temporary external fixation were performed. Antibiotics-impregnated cement beads were impacted on the dead space as the first reconstructive procedure. (C) Follow-up study at one month after plate fixation showed consolidation. (D) Radiographs 3 years later showed exellent bony union. (Clinical eradication of infection was obtained.) A B C D Fig. 2. A 41-year-old male had undertaken IM nailing for open fracture of femoral midshaft after driver's traffic accident, which resulted in nonunion and chronic osteomyelitis with draining sinus. (A) Radiographs on referral. (B) After our debridement, we applied temporary skeletal traction with implantation of antibiotics -impregnated cement beads in the first stage procedure. (C) Rigid IM nailing was done 4 weeks later. (D) Radiographs at two years later after the first stage procedure showed successful union. 우 ) 으로평가하였다. 자료에대한통계적분석은 SPSS 10.0 (Statistical Package for Social Scientists) 를사용하였다. 결과 I군 13예전부와 II군 28예중 26예에서감염의치료와골유합을얻었고, 1예는슬상부절단을시행하였고, 다른 1예는추시가되지않았다 (Fig. 1, 2, 3). 이단계재건술후골소파술, 외고정핀교환과각변형교정술, 피부이식또는근육피판회전술등의보조적시술이 I군은평균 2회이고, II군은평균 6.2회로 I군에서추가시술횟수가적었다. 골유합의판정은방사선촬영상전후 면과측면사진에서골연속성이유지되고체중부하시동통및유동성이없는경우로평균골유합기간은 I군이 19.3주이고 II군이 23.1주로내고정군이더빨랐다. Paley에의한골유합상태는 I군이우수 8예, 양호 5예이었고, II군이우수 18예, 양호 7예, 보통 1예, 불량 2예로 I군과 II군이서로비슷했고 (p=0.492), 기능적평가에서는 I군에서우수 6예, 양호 6예, 보통 1예이었고, II군에서는우수 10예, 양호 13예, 보통 3예, 불량 2예로 I군과 II군이다소비슷한결과를보였다 (p=0.267). 이차수술후감염의재발은 II군의 2예를제외하고는없었다. 재발한 2예의경우한예는첫사고당시에무릎이하절단된상태이고폐색성동맥경화증 (Arteriosclerosis obliterans) 이심한상태여서슬
항생제혼합시멘트정을이용한장관골감염성불유합의이단계치료 399 A B C D Fig. 3. A 29-year-old male had undertaken external fixation for comminuted open fracture of femoral midshaft after driver's traffic accident, which resulted in nonunion and chronic osteomyelitis with draining sinus. (A) Radiographs on referral. (B) Initial hardware removal, meticulous debridement, temporary external fixation, and implantation of antibiotics-impregnated cement beads were done. (C) Microvascularized double-barrel fibular transfer was performed two months later. (D) Radiographs after 26 months showed bony union. 상부절단을시행했고, 나머지한예는자의퇴원한후추시되지않았다. 최종추시결과합병증은 I군에서슬관절강직이 5예 (38%) 로가장많았고, 이에대하여 2예의강압교정술 (Brisement forcee) 과 1예의대퇴사두근성형술 (Quadricepsplasty) 이시행되었다. II군에서는핀주위의감염이 19예 (68%) 로가장흔했고그중 10예에서핀제거술과핀교환술을시행하였다. 17예 (61%) 의슬관절강직이있었고강압교정술만시행한경우가 8예, 대퇴사두근성형술을같이시행한경우가 3예였다. 슬관절강직은수술횟수및외고정장착기간과밀접한연관이있었으며수술횟수가많고외고정기간이길수록더욱강직되었다. 골결손은 I군에서최장 5 cm로평균 2.5 cm 단축이있었고, II군에서는최장 15 cm로평균 2 cm 의단축이있었다. 고찰장관골의감염성불유합의치료목표는감염의근절과골유합의두가지모두를얻는데있다. 감염이치유되지않은상태에서골유합을먼저얻는경우는상당히드물며, 이경우배농이계속되는경우가있어치료결과의예측이어렵다 4,18,20). 저자는감염의제거후골유합을얻는것이보다예측가능한치료방법으로판단하였다 3). 골유합을위한고전적치료방법으로골결손이큰경우에는혈관부착생골이식또는 Ilizarov 골이동술을이용하고, 골결손이적은경우는골감염치료후견고한내고정으로골단축이나부정렬없이골유합을얻는것이다 19). 이들을응용하여저자는이단계재건술을시행하였으며, 일단계수술에서항생제혼합시멘트 정을사용하면장기간국소항생제농도를유지할수있어감염의치유가빠르고동시에장기간항생제주사에따른전신적부작용을감소시킬수있다고알려져있다 2,7,16,17). 이단계수술에서는내고정장치 ( 금속판또는골수강내금속정 ) 또는외고정장치 (Ilizarov 또는 Monofixator) 로각각고정하고필요한경우골내이동술이나골연장술을시행하였다. 감염성불유합의치료에서가장중요한것은골절부의견고한고정을얻는것이며, 감염이있는상태에서도골유합은일어날수있고견고한고정을얻기전감염의활동성을줄이는것이필요하다고하였다 12). 또한 Malgawi는견고한고정이이식골로가는미세혈관의성장에방해를주지않고이식골의골유합을촉진시킨다고한다. 많은저자들이 Ilizarov 외고정기구를사용하면골변형, 골결손, 감염과단축을동시에치료하면서연부조직의위축및관절의구축을방지할수있다고한다 9). 그러나외고정의경우골절부의역학적인고정력이약하여조기체중부하가어렵고인접관절운동의제한과핀삽입부감염등많은문제점을극복하여야한다. 외고정후골수강내금속정으로치환하여고정한경우 17~50% 의감염재발위험이있다고알려져있으나저자의경우철저하고광범위한변연절제술과항생제혼합시멘트정을삽입하여골수강내금속정술후감염의재발이없었다 14). 저자의경우 II군의 28예중 17예 (60%) 에서슬관절굴곡장애가있었고 30도이하의심한운동장애를보인경우도 5예있었다. 슬관절의운동에영향을미치는요소는골절의위치, 연부조직의손상정도, 감염지속기간및섬유조직의형성정도가영향을주지만저자의경험으로감염이오래지속된경우와수술횟수가많았던환자의경우및관절인접핀을삽입한외고정장치도슬관절운동제한에중요한원
400 조세현, 정순택, 박형빈, 황선철, 하용찬, 황인환 인이라고생각한다. Paley의골유합상태및기능적결과는 Ilizarov 장치를이용한경골에사용했던기준으로서다른부위에일률적으로적용하기에는문제점이없지않다. 감염의재발은 II군의 2예에서발생하였는데한예에서는전신적상태가불량하였고, 나머지한예는불충분한사골제거가감염재발의원인이었다고생각된다. 철저하고도광범위한사골절제술과항생제혼합시멘트정의사용이감염재발을줄이는요소이며내고정장치를이용한견고한고정이조기관절운동과빠른골유합을얻을수있는방법으로여겨진다 1,14). 결론본연구에서장관골감염성불유합의치료에항생제혼합시멘트정의효과가관찰되었다. 또한외고정장치를지속하는것보다감염이호전된후가능한조속히견고한내고정장치로교환해주는것이조기관절운동과빠른골유합을얻을수있게해주었다. 참고문헌 1) Alberts KA, Loohagen G and Einarsdottir H: Open tibial fractures: Faster union after unreamed nailing than external fixation. Injury, 30(8): 519-523, 1999. 2) Baker AS and Greenham LW: Release of gentamicin from acrylic bone cement: Elution and diffusion studies. J Bone Joint Surg, 70-A: 1551-1557, 1988. 3) Cho SH, Song HR, Koo KH, Jeong ST and Park YJ: Antibiotic-impregnated cement beads in the treatment of chronic osteomyelitis. Bull Hosp Jt Dis, 56: 140-144, 1997. 4) Dendrinos GK, Kontos S and Lyritsis E: Use of the Ilizarov technique for treatment of nonunion of the tibia associated with infection. J Bone Joint Surg, 77-A: 835-846, 1995. 5) Green SA, Jackson JM, Wall DM, Marinow H and Ishkanian J: Management of segmetal defect by the Ilizarov intercalary bone transport method. Clin Orthop, 280: 136-142, 1992. 6) Gustilo RB, Mendoza RM and Williams DN: Problems in the management of type III (severe) open fractures. A new classification of type III open fractures. J Trauma, 24: 742-746, 1984. 7) Henry SL, Seligson D, Mangio P and Papham GJ: Antibiotic impregnated beads. Part I. Bead implantation versus systemic theraphy. Orthop Rev, 20: 242-247, 1991. 8) Kendall RW, Duncan CP and Beauchamp CP: Bacterial growth on antibiotic-loaded acrylic cement. A prospective in vivo retrieval study. J Arthroplasty, 10: 817-822, 1995. 9) Kim JR, Yang KH and Hwang BY: Treatment of infected nonunion of the tibia by Ilizarov external fixator. J Korean Fracture Soc, 13(4): 921-927, 2000. 10) Klemm K: Antibiotic bead chains. Clin Orthop, 295: 63-76, 1993. 11) May JW, Jupiter JB, Weiland AJ and Byrd HS: Clinical classification of post-traumatic tibial osteomyelitis. Current concepts review. J Bone Joint Surg, 71-A: 1422-1428, 1989. 12) Meyer S, Weiland AJ and Willenegger H: The treatment of infected non-union of fractures of long bones. J Bone Joint Surg, 57-A: 836-842, 1975. 13) Moehring HD, Gravel C, Chapman MW and Olson SA: Comparison of antibiotic beads and intravenous antibiotics in open fractures. Clin Orthop, 372: 254-261, 2000. 14) Nah KH, Park SJ, Han SK, Song HS and Choi NY: Treatment of infected nonunion of long bone shaft. J Korean Fracture Soc, 16(4): 511-518, 2003. 15) Paley D, Catagni MA, Argnani F, Villa A, Bennedetti GB and Cattaneo R: Ilizarov treatment of tibial nonunions with bone loss. Clin Orthop, 241: 146-165, 1989. 16) Papham GJ, Mangino P, Seligson D and Henry SL: Antibiotic impregnated beads. Part II. Factors in antibiotics selection. Orthop Rev, 20: 331-337, 1991. 17) Picknell B, Mizen L and Sutherland R: Antibacterial activity of antibiotics in acrylic bone cement. J Bone Joint Surg, 59-B: 302-307, 1977. 18) Shahcheraghi GH and Bayatpoor A: Infected tibial nonunion. Can J Surg, 37(3): 209-213, 1994. 19) Song HR, Cho SH, Koo KH, Jeong ST, Park YJ and Ko JH: Tibial bone defects treated by internal bone transport using the Ilizarov method. Int Orthop, 22(5): 293-297, 1998. 20) Ueng SWN, Wei FC and Shih CH: Management of large infected tibial defects with antibiotic beads local therapy and staged fibular osteoseptocutaneous free transfer. J Trauma, 43: 268-294, 1997. 21) Weiland AJ, Moore JR and Daniel PK: The efficiency of free tissue transfer in the treatment of osteomyelitis. J Bone Joint Surg, 66-A: 181-193, 1984.