Original Article ISSN 1975-7425(Print) / ISSN: 2288-016X(Online) http://dx.doi.org/10.14777/kjutii.2015.10.1.36 Korean J Urogenit Tract Infect Inflamm 2015;10(1):36-40 Collatamp 를이용한소아수술에서의효용성 유정우, 서영진, 이경섭, 김기호 동국대학교의과대학경주병원비뇨기과학교실 Efficacy of Collatamp on Pediatric Urologic Surgery Jeong Woo Yoo, Yeong Jin Seo, Kyung Seop Lee, Ki Ho Kim Department of Urology, Dongguk University Gyeongju Hospital, Dongguk University College of Medicine, Gyeongju, Korea Purpose: The purpose of this study is to evaluate efficacy of Collatamp (EUSA Pharma [Europe]; a gentamicin-containing collagen implant, GCCI) in pediatric urologic surgery. Materials and Methods: The study comprised a retrospective analysis of 35 consecutive children who underwent pediatric urologic surgery for treatment of hydrocele, undescended testis and varicocele between March 2013 and March 2015. Collatamp containing 130 mg gentamicin and 280 mg collagen were immersed in 300 ml normal saline for up to 6 hours. At set times after immersion the GCCI were removed, the saline diluted in normal human serum and the gentamicin content assayed by a validated immunoassay (Cedia, Microgenics Ltd., UK) to provide an estimate of the loss from each implant. Patients were classified according to two groups: patients with Collatamp (group A) and those without Collatamp (group B). Postoperative complication, operative time and age, etc. were assessed at postoperative 7 days. Results: Sixteen hydrocele, 16 undescended testis, and 3 varicocele patients were identified, with a median age of 87.43±54.10 months, operation time of 103.60±29.41 minutes, and hospitalization period of 3.20±0.68 days. Mean age, operation time, and hospitalization period in group A, B was 64.81±60.32 months, 100.80±46.80 months (p=0.02), 122.30±40.70 minutes, 103.61±29.39 minutes (p=0.17), and 3.20±0.40 days, 3.20±0.80 days (p=0.67), respectively. No statistically significant differences in postoperative complication were observed between the two groups. However, cost was higher in group A than in group B (300,000 won vs, 15,900.82±3,905.72 won). Conclusions: Collatamp may be useful and effective in preventing wound infection in pediatric urologic surgery, although Collatamp is more expensive. Keywords: Testicular hydrocele; Cryptorchidism; Anti-bacterial agents Copyright 2015, Korean Association of Urogenital Tract Infection and Inflammation. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 10 April, 2015 Revised: 22 April, 2015 Accepted: 22 April, 2015 Correspondence to: Ki Ho Kim http://orcid.org/0000-0001-8532-6517 Department of Urology, Dongguk University Gyeongju Hospital, 87 Dongdae-ro, Gyeongju 780-350, Korea Tel: +82-54-770-8265, Fax: +82-54-770-8503 E-mail: honda400uro@gmail.com 36
Jeong Woo Yoo, et al. Efficacy of Collatamp 37 서론 술중창상감염은수술후환자의예후와수술결과에영향을미치며이러한창상감염의예방을위해예방적항생제를사용할수있다. 하지만항생제의오남용은항생제내성을빠르게확산시키며부적절한사용은오히려내성균주의출현및창상감염빈도를증가시킬수있기때문에사용에있어조심하여야한다. 하지만아직까지비뇨기과수술후항생제사용에대한적응증이나치료효과등과같은여러문제들에대해연구가미진한실정이며, 특히소아비뇨기과통원수술환자에서술전, 후항생제사용의효과및부작용에대해서도연구가미진한실정이다. 1 몇몇연구에서술전예방적항생제사용만으로소아비뇨기과통원수술후창상감염을예방할수있다고보고한문헌도있지만, 예방효과가없다는연구들도있다. 다른수술과마찬가지로부적절한항생제사용은내성균증가나관련의료비용의증가등을초래할수있기때문에창상감염예방을위한적절한항생제의적정기간사용은소아비뇨기과통원수술에서도꼭필요할것이다. 창상감염을예방하고줄이기위해이미 Collatamp (a gentamicin-containing collagen implant; EUSA Pharma [Europe], Oxford, UK) 가개발되어골수염, 연조직염과종격염등에사용되고있으며기존정맥주사나경구항생제보다우수함을보고하였다. 2 Collatamp 는 gentamicin 과같은항생제를포함하고있는 collagen implant로서전신적인혈중항생제농도에는영향을주지않으나조직내에삽입되어서서히지속적으로항생제가분비되고술후피부에생길수있는창상감염과같은국소감염을예방하는것으로알려져있다. 3 Gentamicin 은 aminoglycoside계항생제로그람양성균중피부상제균인포도상구균과그람음성균중대장균, 살모넬라균, 및변형균, 녹농균등에효과가있다. 성인에대한수술후 Collatamp의사용은매우안정적이며효과적으로감염을예방할수있는것으로알려져있으나비뇨기과수술, 특히소아비뇨기과수술후안정성에대한논문은부족한상태이다. 본논문은소아비뇨기과수술에있어 Collatamp 의사용이감염예방에도움이되는지, 또한소아비뇨기과수술에있어안전하고효과적인지알아보고자하였다. 대상및방법 2013년 3월부터 2015년 3월까지음낭수종및정류고환, 정계정맥류로진단받은 35명의환아를대상으로하여 Collatamp 의효과및부작용여부에대해서후향적으로분석하였고, 동국대학교경주병원임상시험심의위원회의승인을받았다 (110757-201410-HR-05-01). Collatamp 를사용한군 (group A) 은술전항생제를사용하지않았고, 5 5 cm 크기의 Collatamp를사용하여음낭수종제거술, 고환고정술과정계정맥류절제술을시행하고마지막피부를봉합하기전지방층을봉합한뒤그위에위치시켰으며다음으로피부밑층과피부를봉합하여마무리하였다. 술후항생제는사용하지않았다. Collatamp를사용하지않은군 (group B) 은수술 1시간전에경정맥 2세대 cephalosporin 계항생제를투여하였으며술후경정맥 2세대 cephalosporin 계항생제와퇴원후 5일간경구용 3세대 cephalosporin 계항생제를사용하였다. 모든환아는수술후에는소독약을닦아내고상처밀봉드레싱 (Tegaderm; 3M Healthcare, Maplewood, MN, USA) 을시행하였으며외래경과관찰중한번밀봉드레싱을교체하였고수술일로부터 7일후외래에방문하여치료경과및부작용에대해조사하였다. 통계는 Student t-test 를시행하였으며통계분석은 SPSS ver. 12.0 프로그램 (SPSS Inc., Chcago, IL, USA) 을사용하였으며 p값이 0.05 미만일때통계적으로의미가있는것으로판정하였다. 결 과 음낭수종은 16예, 정류고환은 16예, 정계정맥류 3예였다. 환아의나이는평균 87.43±54.10 개월이었으며수술시간은평균 103.60±29.41분, 입원기간은평균 3.20±0.68일이었다. 음낭수종 16예모두 communicating type이었으며정류고환은 subinguinal type이 14예, retractile type이 2예였다. 전체대상에서수술부위는왼쪽이 19예, 오른쪽이 12예, 양측이 4예였다 (Table 1). Collatamp를사용한군과사용하지않은군의나이, 수술시간, 입원기간은각각 64.81±60.32개월, 100.80±46.80개월 (p=0.02), 122.30±40.70분, 103.61±29.39분 (p=0.17), 그리고 3.20±0.40 일, 3.20±0.80일 (p=0.67) 이었다 (Table 2). 비용적인측면에서는 Collatamp 를사용한군이사용하지않은군에비해더많은비용을지불하였다 (300,000 원 vs. 15,900.82± 3905.72 원 ). Collatamp 를사용한군과사용하지않은군모두 Table 1. Patient characterisitics Variable Value Age (mo) 87.43±54.10 Operation name Hydrocelectomy 16 Orchiopexy 16 Varicocelectomy 3 Operation time (min) 103.60±29.41 Length of stay (d) 3.20±0.68 Values are presented as mean±standard deviation or number only.
38 Jeong Woo Yoo, et al. Efficacy of Collatamp Table 2. Comparison of outcomes of treatment with (group A) and without Collatamp (group B) Variable Group A (n=13) Group B (n=22) p-value Age (mo) 64.81±60.32 100.80±46.80 0.02 Operation time (min) 122.30±40.70 103.61±29.39 0.17 Length of stay (d) 3.20±0.40 3.20±0.80 0.67 Operation 0.24 Varicocelectomy 1 (7.69) 2 (9.10) Hydrocelectomy 4 (30.77) 12 (54.55) Orchiopexy 8 (61.54) 8 (36.36) Complication 0 0 Values are presented as mean±standard deviation, number (%), or number only. 에서합병증은발생하지않았고, 상처감염과같은합병증또한발생하지않았다. 고 찰 수술후창상감염의빈도는약 2.8-7.9% 로원내감염중두번째로흔하게발생한다. 또한전체병원감염중에창상감염이차지하는비율은 14-16% 를차지하며, 이중비뇨기계와연관된병원감염은 9.7% 에달하는것으로알려져있다. 4 하지만이러한창상감염을예방하기위해서, 특히소아비뇨기과수술에있어항생제의과도한사용은항생제에대한내성을증가시킬뿐만아니라창상감염빈도를증가시키고, 더욱강력한항생제또는더많은용량의사용을요하게할수있다. 예방적항생제사용은많은장점이있으나부작용또한가지고있다. 장점으로는예방적항생제를사용함으로써술후생길수있는이환율의감소및입원기간을줄일수있고감염으로인해발생하는비용을줄일수있다. 단점으로는약물부작용및알레르기반응, 혈전정맥염등이발생할수있다. 또한 Clostridium difficile에의한감염을유발할수있으며항생제와관련된과민증과같은매우심각한부작용을야기할수있다. 따라서예방적항생제사용은적절한진료지침에따라야하며, 이를위해항생제사용에따른위험편익분석은꼭필요하다. 5-8 예방적항생제사용에대한장점은비교적명확하지만비뇨기과적수술, 특히소아비뇨기과수술후예방적항생제사용의원칙에대한전반적인연구는부족한실정이다. 예방적항생제사용의목적은술기와관련된감염을방지하고신우신염, 전립선염, 부고환염, 요로패혈증과같은비뇨기계감염을예방하는것이다. 일반적으로예방적항생제사용의적응증은술기의종류와개별환자의위험성여부에달려있다. 또한재수술, 악화된수술전건강상태, 대사기능장애, 특별한위험요인등과같은위험인자들이고려되어야한다. 비뇨기계수술중특히장분절을사용하는시술들, 경직장전립선조직검사 후, 사슴뿔결석제거, 술전재원일이길어진경우, 요폐등과같은특별한상황들에서예방적항생제사용을고려해야한다. 예방적항생제의가장좋은투여시점은수술시작전 30-60 분이며, 수술중합병증이발생한경우에는항생제를즉시투여해야한다. 예방적항생제투여는분할하지않고일회에전량을투여하는것이좋으나수술시간이 3시간이상소요될경우에는항생제를추가로투여하는것이좋다는주장도있으나적극적으로권장되고있지는않다. 9 오염이되거나감염부위를다제거하지못해치료목적으로항생제를사용하는경우외에감염예방목적으로사용하는경우 24시간이상사용은권장되지않는다. 10 창상감염은수술중발생하는오염때문에발생하는것으로서상처봉합후의항생제사용은감염예방에도움이되지않는것으로알려져있으며단기투여및장기투여가동등한효과를보인다고하였다. 11-13 국내의예방적항생제에대한지침은피부절개전 30분또는 1시간이내에비경구로항생제를투여하여수술시점에혈청및조직부위의항생제농도가충분히유지되도록하는것을권고하고있다. 미국의경우도 2005년 Centers for Medicare and Medicaid Services에서발표한가이드라인에따르면심장동맥우회로조성술, 심장수술, 고관절성형술, 슬관절성형술, 대장수술, 자궁절제술, 혈관수술등의수술에서절개 1시간이내에예방적항생제를투여하고수술후 24시간이내에예방적항생제를중단하도록하고있으나, 소아비뇨기과수술에대한항생제관련지침은국내는물론국외에도없는실정이다. 9 미국 22개어린이병원을대상으로분석한연구에서수술전예방적항생제사용의적응증이되는경우와그렇지못한경우각각 82%, 40% 에서항생제를사용하고있었고, 수술종류와병원간에항생제사용비율은큰차이를보이고있는것으로조사되었다. 8 또한소아비뇨기과수술에서도아직까지수술종류에따라통일된예방적항생제지침은없는상태이다. 소아비뇨기과의사들을대상으로한설문조사에서응답자의 85% 이상이개복신우성형술전, 요도하열교정수술후, 또는개복요관방광문합술이나방광재건수술전후에항생제를사용하고있는것으로조사되었다. 음낭수종절제술과고환고정술의경우는수술전에는각각 19.5% 와 26.6% 에서항생제를사용하고있었지만, 포경수술, 단순삭대복원수술, 탈장수술그리고음낭수종절제술에서 90% 이상은수술후항생제를사용하지않았다. 14 국내에서도소아비뇨기과의사들을대상으로소아비뇨기과수술시항생제사용에대한설문조사를한결과고환고정술및서혜부탈장교정술 / 음낭수종절제술의경우수술전각각 60.4% 및 56.6% 에서예방적항생제를사용하고있었고, 수술이후에도각각 90.6%, 92.5% 에서항생제를투여하고있었다. 15 국내소아비뇨기과수술에서예방적항생제사용비율이
Jeong Woo Yoo, et al. Efficacy of Collatamp 39 국외에비해높게조사되는것은아직까지소아비뇨기과수술에서예방적항생제사용에대한적절한가이드라인이없고, 예방적항생제와술후창상감염과의관련성을명확하게보여주는연구들이없기때문에경험적으로국내소아비뇨기과의사들이국외에비해더많이항생제를사용하고있는것으로생각된다. 이런부적절한수술전후예방적항생제오남용은항생제내성균의출현과같은심각한문제를유발할수있기때문에항생제사용기간의단축과같이내성균출현을줄일수있는방법들을모색할필요가있다. 창상감염을줄이고예방하기위해고안된항생제 implant는항생제의전신농도를증가시키지않으면서지역적농도는높은수준으로유지할수있어서항생제내성증가없이창상감염에유용하게사용할수있다. 16 따라서이러한 Collatamp 의사용은경구용이나주사항생제를사용함으로써발생할수있는내성균의증가를막을수있을것으로생각된다. 성인에대한수술후 Collatamp 의사용은매우안정적이며효과적으로감염을예방할수있는것으로알려져있으나비뇨기과수술, 특히소아비뇨기과수술후안정성에대한논문은부족한상태이다. 2 본연구에서는음낭수종및정류고환, 정계정맥류수술을시행한환아중 Collatamp를사용한군과사용하지않은군사이에서입원기간, 수술시간, 그리고합병증에서는차이가없었고, 비용은 Collatamp 를사용한군에서더많은비용이발생하였다. Collatamp 사용군의경우경구나정맥항생제를사용하지않음으로써내성균발생을줄일수있다는기대이익이증가된비용보다더클것으로예측된다. 하지만, 본연구에서수술후 1주일간추적관찰하였을때양군에서합병증이모두없었고, 내성균발생에대해서는확인하지못했다는점은본연구의제한점으로생각되며이를보안할수있는추가연구는꼭필요한부분일것이다. Nam 등 17 은서혜부및음낭수술 ( 고환고정술, 고환절제술, 서혜부탈장교정술및음낭수종절제술 ) 을받은환아 70명을대상으로무작위전향적연구를시행하였는데, 술전항생제사용의상처치료및감염예방효과는술후항생제투여결과와비슷하였고, 오히려항생제투여에따른부작용은술전투여가적어서술전항생제사용만으로충분하다고하였다. 술전항생제를사용하지않고, 창상부위에서만항생제가분비되도록하는 Collatamp의술중사용은소아에게있어술전항생제의사용에비해창상감염의위험은줄이면서항생제전신투여에따른내성균발생을줄일수있고항생제관련과민증들과같은부작용도줄일수있다는장점을가지고있다. 본연구에서 Collatamp 사용유무와상관없이술후피부발적이나상처파열, 발열, 피하감염, 설사등과같은합병증은양군모두에서없었다. 수술전후항생제사용은기본적으로항생제사용에따른내성균발생의위험을가지고있기때문에, 항생제전신농도에는영향을주지않으면서국소적으로수술부위에만 항생제가분비되는 Collatamp의사용은전신항생제사용에버금가는창상감염예방효과를기대하면서항생제사용관련합병증발생을줄이고내성균발생도막을수있는장점을가지기때문에수술과관련된예방적항생제투여방법들중좋은방법이될수있을것으로생각된다. 결론 소아비뇨기과수술후창상감염과같은합병증의예방을위하여예방적항생제를사용하지만얼마나어떻게써야하는지에대한지침은없는실정이다. 이러한예방적항생제를사용함에있어주사제와경구약을이용하는데 Collatamp와같은피부절개부위에서항생제가지속적으로나오는제재를이용하여술후생길수있는피부감염과같은합병증을예방할수있다면주사및경구용항생제를사용하여생길수있는내성균의증가를피할수있고국소적으로상처부위에항생제가도포되어안정적으로술후피부감염을예방할수있을것으로생각된다. CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported. REFERENCES 1. Kanamaru S, Terai A, Ishitoya S, Kunishima Y, Nishiyama H, Segawa T, et al. Assessment of a protocol for prophylactic antibiotics to prevent perioperative infection in urological surgery: a preliminary study. Int J Urol 2004;11:355-63. 2. Chang WK, Srinivasa S, MacCormick AD, Hill AG. Gentamicin-collagen implants to reduce surgical site infection: systematic review and meta-analysis of randomized trials. Ann Surg 2013;258:59-65. 3. Picó RB, Jiménez LA, Sánchez MC, Castelló CH, Bilbao AM, Arias MP, et al. Prospective study comparing the incidence of wound infection following appendectomy for acute appendicitis in children: conventional treatment versus using reabsorbable antibacterial suture or gentamicin-impregnated collagen fleeces. Cir Pediatr 2008;21:199-202. 4. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999;27:97-132; quiz 133-4; discussion 96. 5. Laxenaire MC. Epidemiology of anesthetic anaphylactoid reactions. Fourth multicenter survey (July 1994-December 1996). Ann Fr Anesth Reanim 1999;18:796-809.
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