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1 병원약사회지 (2014), 제 31 권제 4 호 J. Kor. Soc. Health-Syst. Pharm., Vol. 31, No. 4, 898 ~ 907 (2014) 회원학술보고 중환자에서 Dexmedetomidine의 Opioid-Sparing Effect를고려한 Remifentanil 용량조절 한수정, 김형숙, 이정화, 이은숙, 이연주 a, 조영재 a 분당서울대학교병원약제부, 진료부내과 a Dose Adjustment for Remifentanil with Regards to the Opioid- Sparing Effect of Dexmedetomidine in Critically Ill Patients Soo Jung Han, Hyung-Sook Kim, Jeong Hwa Lee, Eunsook Lee, Yeon Joo Lee a and Young-Jae Cho a Department of Pharmacy, Seoul National University Bundang Hospital Division of Pulmonary and Critical Care Medicine, Department of International Medicine, Seoul National University College of Medicine a 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, , Korea Abstract : Background : Since the analgosedation was emerged as an important concept for critically ill patients, the recommendation for a combinational usage of remifentanil and dexmedetomidine as well as its usage has increased. Taking the opioid-sparing effect of dexmedetomidine into account, the dosage of remifentanil can be reduced if the combination of two drugs is used for the purpose of analgosedation which may consequently lead to the reduction of total drug costs. However, no tapering protocol of remifentanil in case of dexmedetomidine combined as sedative drug has been studied yet and there are no cost-effectiveness data for 투고일자 ; 심사완료일자 ; 게재확정일자 교신저자조영재 Tel: lungdrcho@snu.ac.kr

2 한수정 : 중환자에서 Dexmedetomidine 의 Opioid-Sparing Effect 를고려한 Remifentanil 용량조절 the opioid-sparing effect of dexmedetomidine. Methods : A retrospective cohort analysis was done on patients treated with remifentanil and dexmedetomidine at the medical intensive care unit (MICU) of a tertiary teaching hospital from August 2013 to September The success rates of remifentanil reduction and cost reduction of analgesics were analyzed via the data of dosage and costs of remifentanil, dexmedetomidine and other rescue analgesics. Results : Of 63 patients admitted to the MICU, 29 patients were treated with remifentanil and dexmedetomidine for analgosedation under mechanical ventilator care and 10 patients were treated with a half reduced dose of remifentanil. Eight (80%) patients succeeded in reducing their dose of remifentanil since the used Richmond Agitation-Sedation Scale showed scores between-2 and 0 and the numeric rating score for pain was maintained below 5. The rate of cost reduction was 32.8% (from 159,059 to 105,283) in comparing the remifentanil-reduction succeeded group to the failed group (p=0.044). The overall rate of cost reduction was 26.9% in the whole remifentanil-reduction trial group. Conclusions : The dose reduction of remifentanil was successfully achieved in critically ill patients under administration of remifentanil and dexmedetomidine, and it might be cost-effective. This study presents the possibility of an analgosedation adjustment that can be applied to MICU patients treated with both of dexmedetomidine and remifentanil. [Key words] Analgosedation, Dexmedetomidine, Remifentanil, Opioid-sparing effect 연구배경및목적최근미중환자학회의중환자실재원환자에대한진통, 진정및섬망조절에대한임상진료지침 (Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit, 이하미중환자학회지침 ) 1) 이새롭게개정되어발표되었는데, 이번개정내용중중요한핵심의하나는이른바 진통진정 (analgosedation) 의개념이강조된것으로모든중환자실에서는각병원의실정에맞는진통및진정에대한진료지침을갖출것을추천하고있다. 비교적최근에 도입된약제인 remifentanil과 dexmedetomidine이비교적고가의약물임에도불구하고이러한진통및진정지침을기반으로점점더사용빈도가증가하고있으나이두약물을병용하여투여시약물의용량조절에관한연구나지침은전무한실정이다. 마약성진통제중하나인 remifentanil은빠른작용발현과짧은반감기를가지며간기능, 신기능이저하된환자에서도축적이나타나지않는장점이있다. 기계환기적용중인중환자실환자에게추천되는 nonbenzodiazepine계진정제 1) 인 dexmedetomidine은 아편유사제-보존효과 (opioid-sparing effect) 가특징으로, 단기간진정을요구하는경우다른진정제

3 JKSHP, VOL.31, NO.4 (2014) 와비교시실제마약성진통제의요구량을감소시켰으며위약과비교시다른진정제의요구량또한감소시켰다. 2)-7) 특히 dexmedetomidine은 remifentanil 과병용시 remifentanil의사용량감소를기대할수있다는연구또한밝혀져있다. 8),9) Remifentanil과 dexmedetomidine은모두중환자에서진통및진정, 통증조절목적으로투여시현재까지보험급여의대상이아니므로두약제사용시비교적고가인 remifentanil의사용량감소를확인하여적절한감량지침의권장으로이어진다면환자의경제적부담또한경감시킬수있는진통진정이가능할것이다. 이러한배경을바탕으로, 서울대병원전체중환자실의료진은미중환자학회지침을반영하여 remifentani과 dexmedetomidine을기반으로한진통진정지침을개정도입하였다. 이지침의경우 remifentanil 조절단위는 0.05 mcg/kg/min로제시되었으나, 분당서울대병원내과계중환자실 (Seoul National University Bundang Hospital Medical Intensive Care Unit, 이하 SNUBH MICU) 의료진은임상적경험을반영하여 dexmedetomidine을추가한경우일정수준의진통진정상태에도달시 remifentanil 50% 감량항목을추가적용한 SNUBH MICU 진통진정지침을도입하였다. 이를통해 remifentanil과 dexmedetomidine을병용하였을때적절한진통진정을유지하면서진통제의사용량을줄이는보다체 계적인 analgosedation 진료를추구하였고, 이에본연구에서는이러한진통진정진료지침을적용할경우 remifentanil 감량성공여부와비용절감여부를분석하고자하였다. 대상및방법 2013년 8월 1일부터 2013년 9월 30일까지일개대학병원내과계중환자실에입실한환자를대상으로후향적전자의무기록검토를통해연구를시행하였다. 이중기계환기적용시미중환자학회지침을반영한 SNUBH MICU 진통진정지침 (Fig. 1) 에따라 remifentanil과 dexmedetomidine 투여후 Richmond Agitation-Sedation Scale(RASS) - 2~0, Numeric Rating Scale(NRS) 5 미만인경우 remifentanil을절반으로감량한환자를연구에포함하였으며, remifentanil 감량후지속적신경근차단제를투여하였거나 dexmedetomidine 이외의또다른진정제를투여한환자는제외하였다. 조사항목으로환자의특성, 진통진정약제사용현황과 24시간진통진정약가를수집하였다. 환자의특성으로는인구학적변수, 임상적상황에대한변수, Acute Physiology And Chronic Health Evaluation (APACHE) II 점수및중환자실입실이유및주진단, 신기능, 간기능을포함한연구시행당일혈액 1. Analgesics / Sedation 1 remifentanil mcg/kg/min, escalation by 0.05 mcg/kg/min 2 dexmedetomidine mcg/kg/hr (no loading dose) 2. RASS, NRS 또는 CPOT 평가하여 [RASS score: -2~0, NRS<5 or CPOT <3] 인경우 remifentanil 기존용량의절반으로감량 3. 용량조절후 4시간간격 RASS, NRS 또는 CPOT 평가 1 RASS, NRS 또는 CPOT 유지 remifentanil 용량유지또는재감량고려 2 NRS 5 또는 CPOT 3 fentanyl mcg IV bolus q 30 min 3회반복시 remifentanil 기존용량으로증량 Critical Care Pain Observation Tool, CPOT; NRS, Numeric rating scale; RAAS, Richmond Agitation-Sedation Scale Fig. 1 Analgosedation protocol of seoul national university bundang hospital medical intensive care unit (SNUBH MICU)

4 한수정 : 중환자에서 Dexmedetomidine 의 Opioid-Sparing Effect 를고려한 Remifentanil 용량조절 검사결과를조사하였다. 진통진정약제사용현황으로는 remifentanil, dexmedetomidine의사용일수, 용량, remifentanil과 dexmedetomidine 이외의약제사용여부를조사하였으며, 임상결과로는 remifentanil 감량시점의 RASS, NRS 및 Critical Care Pain Observation Tool (CPOT) 10) 을조사하였다 (Table 1). 연구기관의진통진정지침은중환자실환자의진정평가척도인 RASS 0(alert, calm) 에서 -2(light sedation) 인경우진정조절이원활한것으로간주하였다. 환자가스스로통증을수치화시킬수있는경우 NRS를우선으로진통평가에활용하였으며, 이것이불가능할경우 CPOT을통하여통증정도를파악하였다. NRS 5점미만, CPOT 3점미만을유지할때통증조절이이루어진다고보았고, 이와같이진통진정평가를통해적정범주안에속할때 remifentanil 감량을시도한경우를연구대상으로등록하였다. Table 1. Description of the critical-care pain observation tool Indicator Description Score Facial expression No muscular tension observed Relaxed, neutral 0 Body movements Presence of frowning, brow lowering, orbit tightening, and levator contraction All of the above facial movements plus eyelid tightly closed Does not move at all (does not necessarily mean absence of pain) Tense 1 Grimacing 2 Absence of movements 0 Muscle tension Evaluation by passive flexion and extension of upper extremities Compliance with the ventilator (intubated patients) Slow, cautious movements, touching or rubbing the pain site, seeking attention through movements Protection 1 Pulling tube, attempting to sit up, moving limbs/ thrashing, not following commands, striking at staff, Restlessness 2 trying to climb out of bed No resistance to passive movements Relaxed 0 Resistance to passive movements Tense, rigid 1 Strong resistance to passive movements, inability to complete them Alarms not activated, easy ventilation Very tense or rigid 2 Tolerating ventilator or movement Alarms stop spontaneously Coughing but tolerating 1 0 Async hrony: bloc king ventilation, alarms frequently ac tivated Fighting ventilator 2 OR Vocalization (extubated patients) Talking in normal tone or no sound Talking in normal tone or no sound 0 Sighing, moaning Sighing, moaning 1 Crying out, sobbing Crying out, sobbing 2 Total, range

5 JKSHP, VOL.31, NO.4 (2014) Remifentanil 감량후 24시간까지감량한용량을유지한경우를감량성공군으로간주하며, 같은기준시간내에서 remifentanil을재증량한경우감량실패군으로구분하였다. 두군을분석하여 RASS, NRS 정도와아편유사제-보존효과에영향을줄수있는감량당시및전, 후시점에서두약제의용량을조사하였으며, 감량후 24 시간동안의진통진정약가를확인하였다. 이때 remifentanil, dexmedetomidine의약가뿐아니라, 통증평가를통해 rescue fentanyl을투여한경우그약가를포함하여조사하였다. 통계학적으로는 remifentanil 감량성공군과감량실패군의차이를보기위해 Mann-Whitney 검정을이용하였으며, remifentanil 감량시약물용량감소와약가절감을확인하기위해 Wilcoxon signed rank test를이용하였다. 통계분석은 SPSS version 11.0 을통해이루어졌으며, p값이 0.05 미만일때유의성이있는것으로평가하였다. 이연구는본기관의생명윤리심의위원회에서심의를통해후향적연구방법에따른동의서면제를승인받았다. (IRB No. B ) 결과 1. 대상환자의특성연구기간동안내과계중환자실에입실한환자는 63 명이었으며이중 remifentanil과 dexmedetomidine을병용한환자는 29명 (46%) 이었다. 두약제병용환자중제외대상에해당하는환자 19명을제외한 10명을대상으로연구를진행하였다 (Fig. 2). 대상환자 10명의특징과임상결과는 Table 2에요약하였다. 감량성공군은 8명 (80%) 이었으며, 연령, 신장, 체중및중환자실관련지표에서는양군에서유의한차이가없었다. 2. 진통진정약제사용현황양군의 remifentanil과 dexmedetomidine의용량, 사용일수, MICU 입실후경과일수는 Table 3 과같다. Remifentanil 감량시점을기준으로감량성공군은평균 RASS -0.6점, 평균 NRS 0점이었으며감량실 Critical Care Pain Observation Tool, CPOT; NRS, Numeric Rating Scale Fig. 2 Flow chart of study population enrollment

6 한수정 : 중환자에서 Dexmedetomidine 의 Opioid-Sparing Effect 를고려한 Remifentanil 용량조절 Table 2. Clinical characteristics of the enrolled patients* Sex Success group Fail group of of remifentanil remifentanil reduction (n=8) reduction (n=2) M/F 5 / 3 1 / 1 Median age [range] (yr) 68.0 [42-73] 64.5 [61-68] Height(cm) ± ±4.9 Weight(kg) 54.4 ± ± 2.1 Major category of pecialty Respiratory 5 1 Oncologic 3 1 Reasons for ICU admission Respiratory failure 6 1 Intensive monitoring 2 1 CRRT 2 1 ECMO 0 1 APACHE II Score 25.3 ± ± 4.3 ICU days 23.0 ± ± 29.7 Hospital days 83.3 ± ± 53.7 Ventilator days 16.9 ± ± 29.0 Mortality/Survival 3/5 1/1 Val ues ar e expr essed as n and mean ± SD. APACHE, Acute physiology and chronic health evaluation; CRRT, Continuous renal replacement therapy; ECMO, Extracorporeal membrane oxygenation; ICU, Intensive care unit *No significant differences between two groups by Mann-Whitney analysis 패군은평균 RASS -0.5점, 평균 NRS 2점으로나타났다. 감량당시 remifentanil 용량은감량성공군에서는약 0.1 mcg/kg/min이었으며감량실패군에서는 0.07 mcg/kg/min이었다. 감량후 24시간동안의 remifentanil 평균용량은감량성공군의경우절반수준인약 0.05 mcg/kg/min으로감소되었으나감량실패군은 mcg/kg/min에서 mcg/kg/min 수준의감소에그쳤다. 아편유사제-보존효과에영향을줄수있는기여요인으로, dexmedetomidine의용량은감량성공군, 감량실패군순으로감량당시각각 0.34, 0.5 mcg/kg/hr 였으며, 감량후는각각 0.33, 0.49 mcg/kg/hr로감량전후 dexmedetomidine은유지양상이었다. 투여시작시점부터감량직전까지 remifentanil 평균용량의경우감량성공군의경우 mcg/kg /min으로감량실패군 mcg/kg/min에비하여높았으나, 통계적으로유의한차이는없었다. Remifentanil 감량당시 remifentanil 누적사용일수는감량성공군 8일, 감량실패군 8.4일로나타났으며, dexmedetomidine의경우감량성공군이 5.4일, 감량실패군 8.2일로조사되었으나유의미한차이는나타나지않았다. Remifentanil 감량당시중환자실입원일수는감량성공군 13.4일로감량실패군 8.5일보다길었으나통계적으로유의한차이는없었다 시간진통진정약가분석진정진통시총약가정보와, 감량당시의 remifentanil, dexmedetomidine 용량유지를가정했을경우 24시간동안의진통진정약가를 Table 4에나타내었다. 이때진통진정총약가에는 24시간 remifentanil, dexmedetomidine 투여약가및 remifentanil 감량시 NRS 증가로추가된 rescue fentanyl 약가또한포함하였다. Rescue fentanyl 횟수는감량성공군 1.3회, 감량실패군 1.5회였으며이로인한 Fentanyl 투여약가는각각 1,725원, 2,070원이발생하였다. 감량당시의 remifentanil, dexmedetomidine 용량유지를가정하였을경우 24시간동안의진통진정약가는 24시간동안투여된 remifentanil, dexmedetomidine과 rescue fentanyl의약가를합한값으로감량성공군 159,059원, 감량실패군 165,113원이었다. 반면, 실제 remifentanil을감량후 24시간동안의진통진정약가의평균은 102,783원, 164,308 원으로감량성공군의경우 32.8% 의약가절감을나타냈으나감량실패군의경우 0.5% 에그쳤다 (p = 0.044). 이연구에서의전체감량시도환자를기준으로하였을때평균 26.9% 의약가가절감되었으며 (p =

7 JKSHP, VOL.31, NO.4 (2014) Table 3. Comparison of analgosedation drug s status between two groups Success group of remifentanil reduction (n=8) Fail group of remifentanil reduction (n=2) p-value Analysis of RASS -0.6 ± ± analgosedation NRS ± Remifentanil (mcg/kg/min) Dose at reduction ± ± hr average dose after reduction ± ± Average dose before reduction ± ± Cumulative therapy days before reduction 8.0 ± ± Dexmedetomidine (mcg/kg/hr) Dose at reduction 0.34 ± hr average dose after reduction 0.33 ± ± Average dose before reduction 0.38 ± ± Cumulative therapy days before reduction 5.4 ± ± ICU LOS at reduction (days) 13.4 ± ± Val ues ar e expr essed as mean ± SD. ICU, Intensive care unit; LOS, Length of stay; NRS, Numeric rating scale; RAAS, Richmond Agitation-Sedation Scale Table hour-cost of the analgosedation drug according to the remifentanil reduction Average of the reduction of remifentanil Success group of remifentanil reduction (n=8) Fail group of remifentanil reduction (n=2) p-value Rescue fentanyl trial Rescue fentanyl cost (won) 1,725 2, hr analgosedation costs with the dose before reduction (won) [A] 159, , hr analgosedation costs with the dose after reduction (won) [B] 102, , Cost reduction (%) [{(A-B)/A}*100] 32.8% 0.5% Overall cost reduction (%) 26.9% 0.007), 따라서 rescue fentanyl 등의추가약가를고려하더라도 remifentanil의감량이가져오는약가절감의가능성을확인할수있었다. 고찰 연구에서는 remifentanil과 dexmedetomidine 병용시 dexmedetomidine의아편유사제-보존효과를고려하여목표진통진정상태에도달하면투여중이던 remifentanil 용량의 50% 의감량을통한용량조절의성공률및성공여부에영향을줄수있는요인및약가절감효과를분석하였다. 그결과 remi

8 한수정 : 중환자에서 Dexmedetomidine 의 Opioid-Sparing Effect 를고려한 Remifentanil 용량조절 fentanil 감량성공률은 80% 였으며, 감량성공여부와관계없이감량시도를통한약 27% 의약가절감효과를확인할수있었다. Dexmedetomidine은 non-benzodiazepine계진정제로, benzodiazepine에비하여기계환기적용중인중환자실재원환자의더나은임상결과를기대할수있어최근 benzodiazepine을대체할수있는새로운진정제로사용되고있다. 2) 특히, benzodiazepine 에비하여섬망을유발할가능성이낮고, 그로인한중환자실재원기간의단축을가져올수있으며, 또한진통효과를가져아편유사제-보존효과로마약성진통제의절감을기대할수있다는점이그장점이다. 한편 remifentanil은초속효성마약성진통제로간, 신부전상태에서도약물축적이없다는장점이있으나가격부담이높아적정용량의사용이권장되는약물로서, 이에본연구를시행한중환자실에서는일반적인중환자실에서의추천용량보다다소저용량의 remifentanil 투여후추가적진정제가필요할경우 dexmedetomidine을선택함으로써진정효과에더해 remifentanil 감량의이익또한추구하고자하였다. Remifentanil 감량시감량율은문헌마다차이가있지만 remifentanil 단독투여군에서 10~20% 를추천하고있다. 11),12) 중환자실에서아편유사제-보존효과에대한연구를살펴보면, Parran, L. 등은마약성진통제투약일수 5일을기준으로그이하시 3~4일에걸쳐 tapering하고, 그이상투여했을경우투약일수에비례하여 tapering 시간을연장하는방법을제시한바있다. 11) 또한, Franck L. S. 등의연구에서는마약성진통제를투약일수기준에따라 5일이상시일일 20% 씩감량, 14 일이상시일일 10% 씩감량하거나, 7일이상시8시간마다10% 씩감량, 7일이상시 12 시간마다 10% 씩감량하는기준을제안하기도하였다. 12) 연구분석에서 2명의감량실패가있었는데, 이는기존의 remifentanil 투여용량이최대값수준으로높은경우에도 remifentanil 감량율을 50% 로설정한점에서그원인을찾을수있다. 즉, 50% 의감량율은기존 remifentanil의투여용량이높은환자에게는상대적으로넓은간격의약용량감소로이어져진통진정에서의 remifentanil 감량의실패요인이될수있었을 것이다. 또한이연구에서의 remifentanil 감량성공군과감량실패군의 remifentanil 투약일수의평균은각각 8.0일과 8.4일로, 마약성진통제투여일수 7일이상시 8시간간격으로 10% 의 tapering을추천하는 Parran, L. 등의연구 11) 를고려했을때 remifentanil 감량율 50% 가 dexmedetomidine의아편유사제-보존효과를감안하더라도감량비율이과도했을가능성또한존재한다. 현재마약성진통제투여후감량방법에대한구체적인기준은부족하다. 13) 본연구에서는 remifentanil 감량을진통진정평가를통해결정하였는데, 우선적으로중등도의통증에해당하는 NRS 5점미만인경우통증조절이이루어진다고보았다. 본연구의 remifentanil 감량실패군 2명중 1명의경우 NRS 4 점인시점에서 remifentanil 감량을시도한경우였으며, remifentanil 감량성공군 8명중감량당시 NRS 평가가가능했던 6명모두 NRS 0점인점을고려할때 remifentanil 감량기준의 NRS를현재알려진진통진정지침 1) 에서의미있는통증으로정의내린 4점미만으로조정하는것또한고려해야할수있겠다. 본연구에서 remifentanil 감량시점에서의 remifentanil과 dexmedetomidine의용량또는사용일수등이 remifentanil 감량성공률에미치는영향은확인할수없었다. 하지만, dexmedetomidine은용량-반응관계의진정효과를보인다는연구결과 14) 를고려할때, dexmedetomidine의투여용량이높다면 remifentanil의요구량을상대적으로감소시킬가능성이높을것으로예상할수있다. 따라서, dexmedetomidine의유지용량이 remifentanil 감량성공여부의영향인자가될수있다. 또한, 앞서살펴본바와같이 remifentanil 감량시점에서의 remifentanil의용량역시감량성공여부에영향을미칠수있는데, 이는 dexmedetomidine의보완가능한 remifentanil 감량폭에대한연구가부족하기때문으로이러한부분을밝힐수있는추가적인전향적연구가필요할것이다. 선별된환자수에비해등록된환자수가적었던이유로는후향적분석이라는한계와함께진통, 진정및섬망조절에대한임상진료지침 1) 에서추천하는진통

9 JKSHP, VOL.31, NO.4 (2014) 우선진정 (analgesia-first sedation) 의일환으로 remifentanil 단독투여시에도적절한진통진정이유지되었던환자비율이높았던점과신경근차단제및 remifentanil 이외의진통제또는 dexmedetomidine 이외의진정제가투여되었던환자들을제외하였기때문에제한된환자수가등록될수밖에없었다. 또한, 임상관찰기록에서의 NRS 측정이가능했던경우는비교적일관성있는평가가가능하였지만, 이것이불가능할경우 CPOT로통증의조절정도를평가하였다는점에서관측자요인을완전히배제할수는없었던한계가있다. NRS 측정은 4시간간격으로내과계중환자실간호사에의해기록되었는데, 교대근무로이뤄진간호업무의특성으로인해개인간오차가나타날수있을것이다. 하지만, 실제진통진정약제조절의경우주치의 NRS 또는 CPOT 판단에의해이뤄지므로조절당시의상태의판단에있어서개인차에대한오차는적을것으로사료된다. 다만, NRS의경우상주간호사에의해분당서울대병원전자의무기록에시간별측정값을의무적으로기입하고있어모든자료를확인할수있었지만, CPOT의경우의무기록사항에포함되지않아주치의의판단근거로만사용되고기록은생략된경우가많았다. 이에본연구의결과에는 NRS 위주로결과를서술하였다. 이러한한계가있었으나현재까지중환자실에서 dexmedetomidine의아편유사제-보존효과를고려하여이를 remifentanil 용량조절에활용하였던연구는전혀없었다. 따라서본연구는중환자실에서기계환기적용시 remifentanil과 dexmedetomidine 병용환자에서 remifentanil 감량가능성을확인하였고, 그결과를통해 remifentanil과 dexmedetomidine을사용중인환자에서향후 remifentanil 용량조절을적용할수있는기준을제시하였다는데의의를갖는연구라할수있다. 참고문헌 1) Barr J., Fraser G.L., Puntillo K, Ely E.W., Gelinas C., Dasta J.F., Davidson J.E., Devlin J.W., Kress J.P., Joffe A.M., Coursin D.B., Herr D.L., Tung A., Robinson B.R.H., Fontaine D.K., Ramsay M.A., Riker R.R., Sessler C.N., Pun B., Skrobik Y. and Jaeschke R.: Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Critical Care Medicine, 41, (2013) 2) Arain S.R., Ruehlow R.M., Uhrich T.D. and Ebert T.J.: The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg, 98, (2004) 3) Martin E., Ramsay G., Mantz J. and Sum- Ping S.T.: The role of the a2-adrenoceptor agonist dexmedetomidine in postsurgical sedation in the intensive care unit. J Intensive Care Med, 18(1), (2003) 4) Elbaradie S., El Mahalawy F.H. and Solyman A.H.: Dexmedetomidine vs propofol for short-term sedation of postoperative mechanically ventilated patients. J Egypt Natl Canc Inst, 16, (2004) 5) Venn R.M., Bradshaw C.J., Spencer R., Brealey D., Caudwell E., Naughton C., Vedio A, Singer M., Feneck R., Treacher D., Willatts S.M. and Grounds R.M.: Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia, 54, (1999) 6) Triltsch A.E., Welte M., von Homeyer P.,.. Grosse J., Genahr A., Moshirzadeh M., Sidiropoulos A., Konertz W., Kox W.J. and Spies C.D.: Bispectral indexguided sedation with dexmedetomidine in intensive care: a prospective, randomized, double blind, placebo-controlled phase II study. Crit Care Med, 30, (2002) 7) Venn R.M. and Grounds R.M.: Comparison

10 한수정 : 중환자에서 Dexmedetomidine 의 Opioid-Sparing Effect 를고려한 Remifentanil 용량조절 between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth, 87, (2001) 8) Khan Z.P., Ferguson C.N. and Jones R.M.: Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia, 54, (1999) 9) Bhana N., Goa K.L. and McClellan K.J.: Dexmedetomidine. Drugs, 59, (2000) 10) Gelinas C., Fillion L., Puntillo K.A., Viens C. and Fortier M.: Validation of the Critical-Care Pain Observation Tool in Adult Patients. Am J Crit Care, 15, (2006) 11) Parran L. and Pederson C.: Effects of an opioid taper algorithm in hematopoietic progenitor cell transplant recipients. Oncology Nurs Forum, 29, (2002) 12) Franck L.S., Naughton I. and Winter I.: Opioid and benzodiazepine withdrawal symptoms in paediatric intensive care patients. Intensive and Critical Care Nursing, 20, (2004) 13) 이경아, 김수희, 조주희, 안지현, 손은선, 김성은, 석현주 : 원내외과계중환자실재원환자의마약성진통제 tapering 현황분석. 한국병원약사회지, 29(4), (2012) 14) Ebert T.J., Hall J.E., Barney J.A., Uhrich T.D. and Colinco M.D.: The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology, 93(2), (2000)

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar