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1 Korean J Pain Vol. 22, No. 2, 2009 대한통증학회지 2009; 22: DOI: /kjp 종설 척수강내약물주입술 서울대학교의과대학마취통증의학교실 남상건ㆍ김용철 The Intrathecal Drug Administration System Francis Sahngun Nahm, M.D., and Yong Chul Kim, M.D. Department of Anesthesiology and Pain Medicine, Seoul National University School of Medicine, Seoul, Korea The intrathecal drug administration system (ITDAS) has recently been introduced for treating chronic intractable pain patients who have failed with conservative pain treatments. The obvious advantages of its use are the direct intrathecal delivery of drugs, which yields reduced adverse effects and the increased strength of drugs, as compared to its oral or intravenous route. This article offers a review of the ITDAS with a brief review of its evidence-based effectiveness, the technical approach, and the complications. (Korean J Pain 2009; 22: ) Key Words: complication, effectiveness, implantable pump, intrathecal, pain, technique. 서론아편양제제를이용한통증치료에있어중요한점은약제의과도한부작용없이적절한통증조절이가능해야한다는것이다. 그러나경구용모르핀으로치료받고있는환자중약 10-30% 에서는약제의과도한부작용과이에따른부적절한진통작용으로인하여성공적인치료효과가나타나지않는다고보고되고있다. 1) 일반적으로아편양제제의부작용을줄이기위하여아편양제제의종류를변경하고부작용에대한대증적치료를함과동시에전신적인아편양제제의투여를줄이고투여경로를바꾸는등의방법이사용되고있다. 이러한측면에서모르핀을척수강내로투여하게되면경구용량의약 1/300로동일한진통효과를나타낼수있는장점과 2) 운동기능및자율신경기능에영향을끼치지않으면서용량에비례하여진통작용이있고, 날록손에의해길항된다는장점이있다. 여러연구에의해 척수강내로투여된아편양제제가척수후각 (dorsal horn) 의 lamina II III에있는 subtantia gelatinosa에주로작용한다는것이밝혀졌고, substantia gelatinosa에서의아편양제제의작용은침해수용성신경세포들의방전을억제함으로써통증의전달이억제된다고알려져있다. 3) 최근국내에서척수강내약물주입기 (intrathecal drug administration system, ITDAS) 이식술을통한통증조절에관한증례가보고되었고, 4,5) 건강보험심사평가원에서신기술의료행위로인정되어향후이시술의사용이지속적으로증가할것으로여겨져척수강내약물주입술에대하여살펴보고자한다. 본론 1. 역사적배경 1976년동물실험에서척수강내투여된모르핀이강 접수일 :2009 년 7 월 29 일, 승인일 :2009 년 7 월 31 일책임저자 : 김용철, ( ) 서울시종로구연건동 28 서울대학교의과대학마취통증의학교실 Tel: , Fax: pain@snu.ac.kr Received July 29, 2009, Accepted July 31, 2009 Correspondence to: Yong Chul Kim Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, 28, Yeongeon-dong, Jongno-gu, Seoul , Korea Tel: , Fax: pain@snu.ac.kr

2 118 FS Nahm and YC Kim / Korean J Pain Vol. 22, No. 2, 2009 력한진통효과를보였다는보고에 6) 이어 1979년에는인간에서도척수강내로모르핀을주입하면통증이효과적으로감소된다는사실이보고되었다. 7) 1980년대초반에는암성통증환자에게척수강내에직접적으로아편양제제의지속주입으로효과적인진통효과를얻었다는증례가보고되었으며 8,9) 이후모르핀의척수강내투여가암성통증환자의약 66-78% 에서우수한진통효과가나타나며 9,10) 비암성통증환자의 65% 에서도통증감소효과가나타났다는연구결과가 11) 발표되었다. 또한 429명의환자들을대상으로실시한대규모다기관연구에서도척수강내에모르핀의투여가효과적으로통증을감소시킨다는것이확인되었다. 12) 척수강내모르핀투여효과에대한초기의연구들은주로모르핀의지속적주입이아닌일회주입후의효과를평가하였으나, 이런경우는약물의농도가급격하게변하여부작용이많아지고, 반복적인척수천자로인해감염및뇌척수액유출의위험성이높아진다는연구결과가보고되었다. 13) 이에 1982년프로그램이가능한지속주입형매몰식펌프인 Infusaid pump R (Shiley Infusaid, Inc. Norwood, MA) 가최초로상용화된이래, 14) SynchroMed R (Medtronic, Minneapolis, MN) 가미국 FDA 의승인을받았고최근에는 SynchroMed R II가널리쓰여전세계적으로 50,000예이상시술되었다. 15) 2. 근거중심의학에따른 ITDAS를통한통증조절의효과 ITDAS를통한통증조절의효과에대한체계적인고찰들에의하면암성통증및신경병증통증에는강력한근거 (strong evidence) 가있고, 16) 비암성통증의장기간의효과에대해서제한적근거가있다고보고되었다. 17) 비암성통증환자에서 ITDAS를통한통증조절의제한적근거는전향적인무작위연구가어렵기때문에이같은결과가나온것으로보인다. Anderson과 Burchiel은 18) ITDAS를이식한 22명의비암성통증환자를대상으로 2년간추적관찰한연구에서 11명 (50%) 의환자에서최소한 25% 의통증감소와기능향상이나타났다고보고하였고, Angel 등은 19) 척추수술후통증증후군이나신경병증통증을가진총 11명의환자들을대상으로 3년간의추적관찰기간동안 8명 (73%) 의환자에서훌륭한통증감소효과가나타났다고보고하였으며, Hassenbusch 등은 20) 비암성만성통증을가진 18명의환자들을대상으로 5년간추적관찰한결과 11명의환자들에서 39% 의통증감소가있었다고보고하였다. 또한 120명의비암성 통증환자들을대상으로한추적관찰연구에서평균 60% 정도의장기간의통증감소효과가있다고보고되었고, 21) 또다른비암성통증환자들을대상으로한연구에서도 22) 74% 의환자에서평균 60% 의통증감소가있었다고보고하였다. 통증뿐만아니라의식수준및기능적향상도관찰되었는데, 의식수준, 정서, 통증의정도등이 ITDAS를통한통증치료를받고있는환자들에서그렇지않은환자들에비해유의하게향상되었다는보고도있었다. 23) 119명의암성통증환자들을대상으로시행한다기관연구에서는 24) 통증의감소뿐만아니라, 약물의부작용이유의하게감소한다는보고가있었으며, 202명의암성통증환자들을대상으로한무작위대조군연구에서는 25) ITDAS를통한통증치료를받고있는환자들과그렇지않은환자들사이에시술이후첫 12주까지는통증감소효과에있어서유의한차이가있었으나이후에는점차차이가없어지는양상을보이나, 약물의부작용, 피로도, 의식수준등에서는 ITDAS를통한통증치료를받고있는환자들에서그렇지않은환자들에비해유의한차이가있었다고보고하였다. ITDAS를이용한통증조절을위해주로모르핀이이용되지만다른마약성진통제혹은국소마취제등에대해서도연구가이루어졌다. Anderson 등은 26) 지속적인척수강내모르핀주입으로도통증조절이어려운비암성통증환자들을대상으로 hydromorphone 척수강내지속주입을시행한결과모르핀에비해유의한부작용감소와효과적인진통작용을얻을수있었다고보고하였다. 지코노타이드 (ziconotide, Prialt R ) 는비마약성, non- NSAID, 비국소마취제의특성을가지는강력한합성펩타이드로척수의 N-type voltage 칼슘채널길항제로작용하여일차침해수용체로부터의신경전도를차단한다. 27) 지코노타이드는장기간투여시에도아편양제제에서나타나는약물내성이나중독의부작용이나타나지않으며암성통증및비암성통증환자모두에게효과적으로통증조절이가능하다고보고되었다. 28) 부피바카인을아편양제제와혼합하여척수강내에주입할경우아편양제제의내성을줄이면서두약제의상승작용으로암성통증뿐아니라비암성통증에서도효과적인통증조절이가능하다는연구결과도보고되었으며, 29,30) 최근에는 intrathecal cocktails 라는개념이등장하여여러약제를혼합하여 ITDAS를통해투여하기위한시도들도행해지고있다. 31) ITDAS에사용되는약제들에대한연구가지속되고있으나현재까지 ITDAS를위해 FDA의승인을받은약

3 남상건ㆍ김용철 : 척수강내약물주입술 119 제들은황산모르핀, 바클로펜, 지코노타이드뿐이다. 결론적으로다른치료에불응하는암성통증및신경병증통증에는 ITDAS를통한치료를적극적으로고려해볼수있으며일반만성난치성통증의경우아직까지장기적인효과에대해서완전히정립된상태는아니기때문에비용-효과적인측면과시행대상환자의연령등을고려해서시술되어야할것이다. 3. 척수강내에투여된모르핀의약동학모르핀의척수강내주입은척수에존재하는아편양수용체가까이에있는뇌척수액에직접적으로소량의약물을주입함으로써전신적인모르핀사용에따른부작용의상당부분을없애고강한통증억제의효과를가져올수있다. 32) 척수강내모르핀은경막외강내로투여된동일한용량의모르핀보다약 10배강력하다고알려져있으며, 분포용적이 70 ml 정도이기때문에경막외강내주입후혈관을통해흡수되는것보다매우높은농도로뇌척수액내에존재하게된다. 또한뇌척수액에서약물의제거는혈장내에서제거되는것과비슷한속도로제거되는것으로알려져있는데, 이는뇌척수액내에약물이고농도로존재하기때문인것으로추측되고있다. 33) 척수강내로투여된모르핀은척수에공급된혈액에흡수되어통해제거되며 34) 일부는두측확산을통해제거된다. 35) 모르핀의대사산물인 morphine-6-glucuronide (M6G) 은척수강내로투여될경우모르핀에비해큰역할을하는것으로알려져있는데 36) 말초로투여된 M6G는모르핀과비슷한정도의진통작용을나타내지만직접척수강내로투여될경우모르핀에비해 10-45배정도강력하기때문이다. 37) 이는 M6G가혈액-뇌장벽 (blood brain barrier) 을쉽게통과하지못하기때문에말초경로를통해투여하는것보다척수강으로모르핀을직접투여할경우척수강내의 M6G의농도를높일수있어효과적으로통증을조절할수있는장점이있다. 4. 적응증일반적으로 ITDAS 시술은만성적이고보존적인치료에실패한환자들을위하여사용되며적응증은크게암성통증과비암성통증으로나눌수있다. 암성통증환자들은가장일반적인 ITDAS 시술의적응증이다. 예를들어병의초기에는경구용아편양제제로통증이잘조절되나병의진행으로인하여통증이점차증가하고이에따라아편양제제의용량을증가하여약제의부작용 이심하게나타날경우등이 ITDAS 시술의좋은적응증이라고할수있다. 각나라마다차이는있겠지만미국의한연구에서는 ITDAS를통한통증조절이암성통증의경우 3-6개월이상, 비암성통증의경우 11-22개월이상사용할경우비용대비효과가높은것으로나타났다. 38) 일반적으로기대여명이 6개월이상인말기암환자들에게 ITDAS를통한통증조절이추천되고있고 39) 기대여명이 6개월미만인경우는시술로인한이득과위험을잘비교하여시술을결정하여야한다. ITDAS를통한통증조절을시행하는비암성통증의예로는고식적인치료에반응하지않는만성통증으로, Raphael 등은 32) 척추수술후통증증후군이나만성배부통을호소하는환자들에있어척수자극술보다유용하다고보고하였으며이밖에도신경병증통증, 중축성척추통증, 복합부위통증증후군, 말초신경병증, 전신통증등도적응증이다. 40) 신경병증성통증을가진환자보다체성통증양상을호소하는환자에서더좋은효과를나타냈다는보고가있으며, 12) 암성통증과는달리비암성통증환자들에서 ITDAS 이식술은약물중독, 남용, 내성에대한우려와장기간의효용성에대한문제가제기되고있다. 41) 5. 시술전검사 ITDAS를영구적으로이식하기전에효과가있는지판정하기위해사전검사를시행해야하며세심한환자선택이 ITDAS를통한통증조절의성공적인결과를위해매우중요하다. 사전검사에앞서환자에게약물중독, 이차적이득등의문제가없는지에대한신경정신과적평가가선행되어야하며, 이러한문제가모두배제된후사전검사를실시하도록한다. 사전검사의방법은척수강내또는경막외강으로약제를주입하게되며, 일회투여하거나반복적으로투여할수도있고, 지속주입법을사용할수도있다. 척수강내로약제를투여하는방법은 mg의모르핀을일회주입하거나몇일의간격을두고수차례반복적으로주입할수도있고, 척수강내카테터를거치시킨후 mg/hour 의속도로모르핀을지속주입할수도있다. 지속주입하는경우통증이소실될때가지 12-24시간간격으로용량을증량한다. 42) 경막외주입방법을이용할경우척수강내로투여하는용량의 10배를경막외강에일회주입법, 반복주입법, 카테터를이용한지속주입법을이용하여경막외강에약제를투여하면된다. ITDAS를통한통증조절을위한이상적인환자는시험기간동안최소 50% 이상의통증감소가있으면서견딜수있는범위의

120 FS Nahm and YC Kim / Korean J Pain Vol. 22, No. 2, 2009 Fig. 1. Schematic illustrations of exterior (A) and interior (B) of intrathecal pump.

The drug moves from the pump reservoir, through the pump tubing and catheter port, to the infusion site (Courtesy of Medtronic Inc.). 부작용이어야한다.

사전검사에서만족할만한통증감소가없거나참을수없을정도의부작용이관찰되면 ITDAS의영구이식은고려하지말아야하며, 환자에따른개별적인차이가존재할수있으므로충분한기간동안의관찰이필수적이다. 사전검사동안기존에복용하던진통제를중지하는경우금단증상으로인해서효과판정이어려울수있으므로계속복용시켜야한다.

4 120 FS Nahm and YC Kim / Korean J Pain Vol. 22, No. 2, 2009 Fig. 1. Schematic illustrations of exterior (A) and interior (B) of intrathecal pump. The catheter access port allows injection of drug directly into the implanted catheter for drug administration or diagnostic purpose. The drug moves from the pump reservoir, through the pump tubing and catheter port, to the infusion site (Courtesy of Medtronic Inc.). 부작용이어야한다. 43) 저자들의경우한국인의체형이서양인에비해작다는점을고려하여문헌에나타난용량의 60% 정도를투여하는데, 황산모르핀 3 mg을생리식염수에희석하여총 10 ml를경막외강내로주입하는방법을사용하고있다. 사전검사에서만족할만한통증감소가없거나참을수없을정도의부작용이관찰되면 ITDAS의영구이식은고려하지말아야하며, 환자에따른개별적인차이가존재할수있으므로충분한기간동안의관찰이필수적이다. 사전검사동안기존에복용하던진통제를중지하는경우금단증상으로인해서효과판정이어려울수있으므로계속복용시켜야한다. 15) 사전검사를위해척수강내혹은경막외강내로모르핀이투여된이후환자는맥박산소포화도감시, 신경학적검사를실시해야한다. 척수강내로투여된수용성모르핀은투여후약 30분- 1시간후약효가나타나기시작하여 18-24시간동안지속되기때문에 44) 이기간동안지속적인환자감시가반드시필요하다. 6. ITDAS의구조 ITDAS는크게 1 약물저장소, 2 내부튜브, 3 catheter access port, 4 카테터등네부분으로이루어져있다 (Fig. 1). 약물저장소와내부튜브에는환자에게투여되는약물이채워지며, catheter access port는펌프의내부를통하지않고직접카테터와연결되는부분으로환자에게과용량이투여된경우카테터내부의약물을흡인해내거나카테터의막힘등을검사하기위해카테터를통하여척수강내에조영제를직접주입하는경우사용되는통로가된다. 7. 시술방법 1) 펌프의준비 : 펌프를개봉하기전 calibration con- Fig. 2. A spinal puncture needle and an intrathecal catheter. stant가정확한지확인한다. Calibration constant가부정확할경우임상적으로유의한저용량혹은고용량이환자에게투여될위험이있다. Calibration constant가정확하다면펌프에채워져있는생리식염수를주사기로흡인하여버리고투여하고자하는약물을채운후 catheter access port를생리식염수로채워공기를없앤다. 2) 척수강내카테터삽입 : 혈압계, 심전도, 맥박산소포화도등의감시장치를부착하고측와위를취한뒤국소마취혹은전신마취하에시술을시행한다. 요추 4번 pedicle 내측경계면부위에 5 cm 정도의피부를절개하고노출된조직을통해방사선투시하에방정중법으로시술키트에서제공된척추천자용바늘 (Fig. 2) 을척수강내로삽입한다. 삽입된바늘을통하여뇌척수액이유출되는것을확인하고카테터 (Fig. 2) 를삽입하여카테터의끝이흉추 11번정도의높이에위치하도록한다. 지용성약제를사용하는경우카테터끝의위치가통증부위

5 남상건ㆍ김용철 : 척수강내약물주입술 121 에가깝게위치하도록하는것이더욱좋지만, 수용성인모르핀의경우반드시그럴필요는없다. 15) 카테터내부에있는유도철사와척추천자바늘을동시에제거하고카테터를통해뇌척수액이유출되는지다시확인한후시술중에뇌척수액의유출을방지하기위해카테터의끝부분을겸자로막아둔다. 카테터를고정하기위해비흡수성봉합사를이용하여앵커를근막에고정한다. 3) 피하펌프매몰및카테터연결 : 펌프의위치를좌우하복부중어느쪽에위치시킬것인가를결정한후환자가앉은자세에서늑골하연혹은장골능에펌프가닿지않게위치하도록한다. 좌측혹은우측하복부피부에 10 cm 정도의피부절개를가하고펌프가매몰되기에충분한크기의피하포켓을만든다. 이때절개반흔에의해펌프의 refill port가가려지지않도록펌프를위치시키는것이중요하다. 또한펌프가너무깊게매몰될경우펌프의상태파악및용량조절을위한원격조절기가펌프를인식하지못할수있고약제의리필이어려울수있으므로피하 2.5 cm보다깊게매몰해서는안된다. 피하포켓이완성되면터널링기구를사용하여펌프포켓으로부터등절개부위까지피하터널을만들고척수강내에삽입한카테터를펌프포켓까지빼낸다. 피하터널을통과한카테터를적당한길이가되도록불필요한길이를잘라내도록하며, 이때잘라진길이를측정하여남은부분의카테터총길이와카테터내의용적을확인하는것이중요하다. 이후카테터에 connector를끼워펌프본체와연결시키고연결부위가빠지지않도록비흡수성봉합사로다시한번고정하고펌프를포켓에거치시킨다. 펌프가포켓내에서움직이지않도록하기위해비흡수성봉합사로펌프에있는고정용고리 (Fig. 1) 들을복부근막에고정하고절개부위를봉합한다. 4) 프로그래밍 : ITDAS의이식이끝나면원격조정기를이용하여환자의정보, 카테터모델번호, 실제로삽입된카테터의길이, 투여되는약물의성분및농도, 저장된약물의용적등을입력한다. 하루총투여량의결정시아편양제제의전신적투여에서척수강내투여로의완전한전환은금단증상을야기할수있으므로경구투여량의 50% 를척수강내투여용량으로바꾸어투여하며나머지경구투여량은매일 20% 씩줄이면서등가의척수강내용량으로전환시킨다. 45) 최종적으로환자가기존에복용하던경구용아편양제제의총용량이척수강내로투여되도록하며이후에는필요할경우는외래진찰시에환자의반응에따라증량하도록한다. 8. 부작용척수강내로투여된아편양제제로인한부작용중일시적인요저류가가장흔한합병증으로보고되고있으나장기간의방광기능이상은발생하지않으며, 그밖에가려움증, 발한, 체중증가, 성호르몬감소로인한성욕감퇴, 말초부종등이보고되어있다. 46,47) 시술과관련된합병증으로는경막외강혹은척수강내의혈종, 수막염, 경막외농양, 뇌척수액누출로인한두통, 펌프포켓의 seroma 등이있다. 32) ITDAS의기기와관련된합병증으로는카테터에의한과통각, 카테터끝에발생하는육아종성종괴, 뇌척수액의누출로인한두통, 카테터의꼬임, 분리등이발생할수있다. 15,48) 뇌척수액누출로두통의치료를위해자가혈액봉합술을실시할수있으며, 49) 이경우카테터의손상을피하기위해카테터가경막을천자한부위혹은바로두측에서천자를시행하는것이바람직하다. 9. 약물의리필모르핀과 ITDAS의카테터와접촉시 90일이후모르핀의안정성이감소하며, 펌프내에저장되는경우 180 일이후에는안정성이감소하는것으로보고되어있어, 90일주기로새로약물을리필하는것이추천되고있다. 50) 또한펌프내의약물이 1 ml 이하로남게되면펌프의주입속도가급격히감소하게되어저용량투여로인한금단증상이나타날수있으므로펌프내에 1 ml 이상의약제가남아있는상태에서리필을실시해야한다. 50) 따라서미리경보음을설정해두어야하며보통펌프내에 2 ml의약제가남았을때경보음이울리도록설정해두면된다. 리필은펌프가삽입된부위의피부를소독하고리필용 template를이용하여리필용주입구의위치를확인한후주사기에연결된 22게이지바늘을주입구에삽입한다. 주사기를이용하여펌프에남아있는약물을흡인하여버리고, 새약물을주입한다. 22게이지바늘과주사기사이에 clamp가부착된연결튜브를이용하여리필조작시펌프내로공기가들어가지않도록해야한다. 결론 ITDAS를통한통증조절은기존의치료법으로통증이조절되지않는환자에게서약제부작용을줄이면서효과적으로아편양제제를투여할수있는새로운치료

6 122 FS Nahm and YC Kim / Korean J Pain Vol. 22, No. 2, 2009 법으로향후여명이 6개월이상인암성통증환자및다양한치료에반응하지않는난치성의만성비암성통증환자의삶의질향상에크게도움이될수있을것으로생각한다. 참고문헌 1. Expert Working Group of the European Association for Palliative Care: Morphine in cancer pain: modes of administration. BMJ 1996; 312: Sylvester RK, Lindsay SM, Schauer C: The conversion challenge: from intrathecal to oral morphine. Am J Hosp Palliat Care 2004; 21: Yaksh TL, Rudy TA: Narcotic analgestics: CNS sites and mechanisms of action as revealed by intracerebral injection techniques. Pain 1978; 4: Lee SJ, Nam SK, Kim JH, Kim HJ, Lee SC, Kim YC: Implantation of an intrathecal drug administration system: a report of two cases. Korean J Pain 2009; 22: Seo KS, Han KR, Kim SY, Park KE, Kim C: Implantable Intrathecal drug delivery pump in complex regional pain syndrome patient: a case report. Korean J Pain 2009; 22: Yaksh TL, Rudy TA: Analgesia mediated by a direct spinal action of narcotics. Science 1976; 192: Wang JK, Nauss LA, Thomas JE: Pain relief by intrathecally applied morphine in man. Anesthesiology 1979; 50: Onofrio BM, Yaksh TL, Arnold PG: Continuous low-dose intrathecal morphine administration in the treatment of chronic pain of malignant origin. Mayo Clin Proc 1981; 56: Leavens ME, Hill CS Jr, Cech DA, Weyland JB, Weston JS: Intrathecal and intraventricular morphine for pain in cancer patients: initial study. J Neurosurg 1982; 56: Rico RC, Hobika GH, Avellanosa AM, Trudnowski RJ, Rempel J, West CR: Use of intrathecal and epidural morphine for pain relief in patients with malignant diseases: a preliminary report. J Med 1982; 13: Auld AW, Maki-Jokela A, Murdoch DM: Intraspinal narcotic analgesia in the treatment of chronic pain. Spine 1985; 10: Paice JA, Penn RD, Shott S: Intraspinal morphine for chronic pain: a retrospective, multicenter study. J Pain Symptom Manage 1996; 11: Brazenor GA: Long term intrathecal administration of morphine: a comparison of bolus injection via reservoir with continuous infusion by implanted pump. Neurosurgery 1987; 21: Johnston J, Reich S, Bailey A, Sluetz J: Shiley INFUSAID Pump technology. Ann N Y Acad Sci 1988; 531: Belverud S, Mogilner A, Schulder M: Intrathecal pumps. Neurotherapeutics 2008; 5: Smith HS, Deer TR, Staats PS, Singh V, Sehgal N, Cordner H: Intrathecal drug delivery. Pain Physician 2008; 11(Suppl): Patel VB, Manchikanti L, Singh V, Schultz DM, Hayek SM, Smith HS: Systematic review of intrathecal infusion systems for long-term management of chronic non-cancer pain. Pain Physician 2009; 12: Anderson VC, Burchiel KJ: A prospective study of longterm intrathecal morphine in the management of chronic nonmalignant pain. Neurosurgery 1999; 44: Angel IF, Gould HJ Jr, Carey ME: Intrathecal morphine pump as a treatment option in chronic pain of nonmalignant origin. Surg Neurol 1998; 49: Hassenbusch SJ, Stanton-Hicks M, Covington EC, Walsh JG, Guthrey DS: Long-term intraspinal infusions of opioids in the treatment of neuropathic pain. J Pain Symptom Manage 1995; 10: Winkelmuller M, Winkelmuller W: Long-term effects of continuous intrathecal opioid treatment in chronic pain of nonmalignant etiology. J Neurosurg 1996; 85: Roberts LJ, Finch PM, Goucke CR, Price LM: Outcome of intrathecal opioids in chronic non-cancer pain. Eur J Pain 2001; 5: Thimineur MA, Kravitz E, Vodapally MS: Intrathecal opioid treatment for chronic non-malignant pain: a 3-year prospective study. Pain 2004; 109: Rauck RL, Cherry D, Boyer MF, Kosek P, Dunn J, Alo K: Long-term intrathecal opioid therapy with a patient-activated, implanted delivery system for the treatment of refractory cancer pain. J Pain 2003; 4: Smith TJ, Coyne PJ, Staats PS, Deer T, Stearns LJ, Rauck RL, et al: An implantable drug delivery system (IDDS) for refractory cancer pain provides sustained pain control, less drug-related toxicity, and possibly better survival compared with comprehensive medical management (CMM). Ann Oncol 2005; 16: Anderson VC, Cooke B, Burchiel KJ: Intrathecal hydromorphone for chronic nonmalignant pain: a retrospective study. Pain Med 2001; 2: Doggrell SA: Intrathecal ziconotide for refractory pain. Expert Opin Investig Drugs 2004; 13: Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, et al: Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA 2004; 291: Van Dongen RT, Crul BJ, van Egmond J: Intrathecal coadministration of bupivacaine diminishes morphine dose progression during long-term intrathecal infusion in cancer patients. Clin J Pain 1999; 15: Deer TR, Caraway DL, Kim CK, Dempsey CD, Stewart CD, McNeil KF: Clinical experience with intrathecal bupivacaine in combination with opioid for the treatment of chronic pain related to failed back surgery syndrome and

7 남상건ㆍ김용철 : 척수강내약물주입술 123 metastatic cancer pain of the spine. Spine J 2002; 2: Classen AM, Wimbish GH, Kupiec TC: Stability of admixture containing morphine sulfate, bupivacaine hydrochloride, and clonidine hydrochloride in an implantable infusion system. J Pain Symptom Manage 2004; 28: Raphael JH, Southall JL, Gnanadurai TV, Treharne GJ, Kitas GD: Long-term experience with implanted intrathecal drug administration systems for failed back syndrome and chronic mechanical low back pain. BMC Musculoskelet Disord 2002; 3: Nordberg G, Hedner T, Mellstrand T, Dahlström B: Pharmacokinetic aspects of intrathecal morphine analgesia. Anesthesiology 1984; 60: Moore A, Bullingham R, McQuay H, Allen M, Baldwin D, Cole A: Spinal fluid kinetics of morphine and heroin. Clin Pharmacol Ther 1984; 35: Payne R, Inturrisi CE: CSF distribution of morphine, methadone and sucrose after intrathecal injection. Life Sci 1985; 37: Faura CC, Collins SL, Moore RA, McQuay HJ: Systematic review of factors affecting the ratios of morphine and its major metabolites. Pain 1998; 74: Pasternak GW, Bodnar RJ, Clark JA, Inturrisi CE: Morphine-6-glucuronide, a potent mu agonist. Life Sci 1987; 41: Hassenbusch SJ, Paice JA, Patt RB, Bedder MD, Bell GK: Clinical realities and economic considerations: economics of intrathecal therapy. J Pain Symptom Manage 1997; 14(3 Suppl): Hassenbusch SJ: Cost modeling for alternate routes of administration of opioids for cancer pain. Oncology (Williston Park) 1999; 13(5 Suppl 2): Koulousakis A, Kuchta J, Bayarassou A, Sturm V: Intrathecal opioids for intractable pain syndromes. Acta Neurochir Suppl 2007; 97(Pt 1): Kumar K, Kelly M, Pirlot T: Continuous intrathecal morphine treatment for chronic pain of nonmalignant etiology: long-term benefits and efficacy. Surg Neurol 2001; 55: Medtronic Inc: Medtronic Synchromed II programmable infusion system clinical reference guide: pain management Krames ES, Olson K: Clinical realities and economic considerations: patient selection in intrathecal therapy. J Pain Symptom Manage 1997; 14(3 Suppl): France JC, Jorgenson SS, Lowe TG, Dwyer AP: The use of intrathecal morphine for analgesia after posterolateral lumbar fusion: a prospective, double-blind, randomized study. Spine 1997; 22: Krames ES: Intrathecal infusional therapies for intractable pain: patient management guidelines. J Pain Symptom Manage 1993; 8: Yaksh TL, Onofrio BM: Retrospective consideration of the doses of morphine given intrathecally by chronic infusion in 163 patients by 19 physicians. Pain 1987; 31: Ruan X: Drug-related side effects of long-term intrathecal morphine therapy. Pain Physician 2007; 10: Miele VJ, Price KO, Bloomfield S, Hogg J, Bailes JE: A review of intrathecal morphine therapy related granulomas. Eur J Pain 2006; 10: Singh PK, Jain R, Mishra S, Kumar S, Bhatnagar S, Deo S: Management of pericatheter cerebrospinal fluid leak after intrathecal implantation of a drug delivery system. Am J Hosp Palliat Care 2008; 25: Medtronic Inc: Medtronic Synchromed II programmable infusion system clinical reference guide: surgical procedures

Lumbar spine

Lumbar spine CT 32 111 DOI : 10.3831/KPI.2010.13.2.111 Lumbar Spine CT 32 Received : 10. 05. 23 Revised : 10. 06. 04 Accepted : 10. 06. 11 Key Words: Disc herniation, CT scan, Clinical analysis The Clinical