http://dx.doi.org/10.7180/kmj.2013.28.2.137 KMJ Original Article A Comparison of the Recovery Characteristics between Propofol-remifentil and Sevoflurane-remifentail Anesthesia for Total Thyroidectomy Dong Hee Kang, Jeong Gil Lee, Hyeong Ju Jung, Ju Deok Kim, Soo Bong Yu, Si Jeong Ryu, Gyeong Han Kim, Doo Sik Kim Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University, Busan, Korea 갑상선전절제술시 Propofol-remifentanil 과 Sevoflurane-remifentanil 마취의회복양상의비교 강동희 이정길 정형주 김주덕 유수봉 류시정 김경한 김두식 고신대학교의과대학마취통증의학교실 Objectives: This study was investigated the recovery characteristics of propofol-remifentanil and sevoflurane-remifentanil anesthesia for total thyroidectomy Methods: Eighty patients in ASA physical status 1 and 2 scheduled for total thyroidectomy were allocated randomly to either group P (n = 40) or group S (n = 40). Anesthesia was maintained with remifentanil effect site concentration (Ce) 1-3 ng/ml and propofol Ce 2-4 μg/ml in the group P, and was maintained with remifentanil Ce 1-3 ng/ml and sevoflurane 1.5-2% in the group S. Blood pressure, heart rate, and bispectral (BIS) index were measured during perioperative period. The times from discontinuance of anesthetic agent to eye opening, to extubation, and to stating name were measured. Postoperative complications were evaluated. Results: There were no significant differences between group P and S on the blood pressure, heart rate, and recovery time. BIS index of group P showed lower than that of group S during operation (P < 0.05). The incidences of side effects were similar in the two groups, though the incidence of nausea was higher in the group S (P < 0.05). Conclusions: Propofol-remifentanil anesthesia was more advantageous than sevoflurane-remifentanil anesthesia for thyroidectomy in view of side effect incidences. Key Words: Propofol, Remifentanil, Sevoflurane, Total thyroidectomy 우리나라에서갑상선암은발생빈도가빠르게증가하는추세로가장호발하는암이며, 특히여성에서는발생빈도가이전 10년동안연평균증가율이 24.5% 에달하고있다. 1 이에갑상선절제술은과거에비해서수술장안에서매우흔하게볼수있는수술이되었다. 갑상선절제술은피부절개는작지만수술중기도를 직접자극하기때문에충분한마취심도를유지해야한다. 또한수술을마치고각성과회복과정에서수술부위에과도한자극이가해지면출혈을유발할수있고혈종에의한기도폐쇄와같은심각한부작용으로도이어질수있다. 2 따라서수술후각성과회복과정에서일어날수있는오심과구토 (postoperative nausea and vomiting, Corresponding Author: Doo Sik Kim, Department of Anesthesiology and Pain Medicine, College of Medicine, Kosin University, 34 Amnam-dong, Seo-gu, Busan, 602-702, Korea TEL: +82-51-990-6627 FAX: +82-51-254-2504 E-mail: kds0728@chol.com Received: March 12, 2013 Revised: May 16, 2013 Accepted: June 26, 2013 137
PONV), 기침, 통증, 후두경련과같은문제를미리예방하는것이중요하다. 특히 PONV 는전신마취를받은환자의약 30% 에서발생하는데, 갑상선절제술에서는발생빈도가 51-64% 로더욱높게보고되며, 3-4 수술만족도의감소와입원기간증가로인해의료비를증가시킨다. 5 비교적최근에임상에도입되어흔하게사용되는마취제로흡입마취제인 sevoflurane 과정맥마취제인 propofol이있다. Sevoflurane 은혈액-가스용해도가 0.65로낮아서마취유도와각성이빠르며, 마취심도조절이쉽다. 6 또한다른흡입마취제와는달리기도자극이없고, 달콤한냄새가나는특징이있다. 7 Propofol 은빠른효과처평형시간과짧은상황민감성반감기 (context-sensitive half time) 로마취도입이빠르며진정작용으로부터의회복이신속하기때문에, 전정맥마취 (total intravenous anesthesia, TIVA) 에널리사용되고있다. 8 또한 propofol 은기존의흡입마취제와비교했을때수술후항구토효과를보인다는연구결과가많다. 9 Sevoflurane 이나 propofol 과함께적절한제통효과를위해아편유사제를사용해서균형마취를시행할수있는데, remifentanil 이아편유사제중가장짧은상황민감성반감기를갖고있기때문에많이사용된다. 본연구에서는전신마취하에갑상선절제술을받는환자를대상으로흡입마취제인 sevoflurane 에 remifentanil 을함께사용하는마취방법과정맥마취제인 propofol 에 remifentanil 을함께사용하는마취방법간에마취유지와회복시발생하는합병증에차이가있는지알아보고자하였다. 연구대상및방법 전신마취하에갑상선전절제술이계획된환자중미국마취과학회신체등급분류 1-2 에해당하는 25-60 세남녀환자 80명을대상으로하였다. 본연구에대하여본원의임상연구윤리위원회의승인을받고, 술전방문에서환자에게연구의목적과방법에대해충분한설명을하고동의를받았다. 심장질환, 호흡기계질환, 간질환, 신질환, 신경계이상환자, 비만인경우나임신환자, 과거멀미나오심 구토의과거력이있는환자는본연구대상에서제외하였다. 대상환자는무작위로 40 명씩두군으로나누었다. Profopol 과 remifentanil 을이용해마취를유지한군을 P군, sevoflurane과 remifentanil 을이용해마취를유지하는군을 S군으로하였다. 두군간의나이, 성별, 키, 몸무게, 마취시간은차이가없었다 (Table 1). 모든환자는마취전투약은하지않고, 18 G 바늘로정맥로를확보하고수술실에도착하였다. 환자가수술실에도착후심전도, 비침습성혈압감시장치, 맥박산소계측기를부착하였다. 환자의진정수준을감시하기위해서 bispectral index (BISTM, Vista, USA) 감지기를이마에부착하고, 간섭현상없이 BIS 수치가일정하게유지되는것을확인하였다. 기본환자감시장치를적용후 glycopyrrolate (Mobinul TM, Myungmoon, Korea) 0.2 mg 를정맥투여하고 100% 산소 5 L/min 으로심호흡 4번과 1분간의자발호흡으로전산소화를시행하였다. 전산소화후 P군은목표농도조절주입 (target concentration infusion, TCI) pump (Ochestra base premea, France) 를이용하여 remifentanil (Ultiva TM, GSK, Table 1. Characteristics of patients Group P (n = 40) Group S (n = 40) Age (yr) 039.2 ± 8.2 041.5 ± 7.5 Sex (M/F) 0005/35 0007/33 Height (cm) 163.7 ± 6.5 161.4 ± 6.7 Weight (kg) 060.6 ± 5.5 057.9 ± 7.2 Duration of anesthesia (min) 143.7 ± 23.5 155.1 ± 19.8 Values are mean ± SD. Group P, propofol and remifentanil; Group S, sevoflurane and remifentanil. There were no differences between two groups. 138
A Comparison of the Recovery Characteristics between Propofol-remifentil and Sevoflurane-remifentail Anesthesia for Total Thyroidectomy Italy) 의효과처농도를 3.0 ng/ml 로설정하고투여를시작하였다. Remifentanil 이목표농도에도달한후 propofol (Provive TM, Claris, India) 의효과처농도를 4 μg/ml 로설정하여투여하였다. 약제투여후구두명령에대한환자의반응이소실된것을확인하고 rocuronium bromide (Esmeron R, Organon, Netherland) 0.8 mg/kg 를 10 초동안정맥투여하고 90 초경과후기관내삽관하였다. S군은전산소화후 TCI pump를이용하여 remifentanil 의효과처농도를 3.0 ng/ml 로설정하여투여하고목표농도에도달한후 propofol 1.5 mg/kg 을투여하였다. 의식소실을확인하고 rocuronium 0.8 mg/kg 을 10초동안정맥투여뒤 90초경과후삽관하였다. 기관내삽관을한후 FiO 2 0.5 (O 2 1.5 L/min, Air 2.5 L/min) 를공급하면서호기말 CO 2 가 25-35 mmhg 를유지하도록기계환기를시행하였다. 적절한마취심도유지를위해혈압및심박수의변화가마취전측정값의 20% 이내로유지되도록마취약제를조절하였다. P군은 propofol 의효과처농도를 2-4 μg/ml로, remifentanil 의효과처농도를 1-3 ng/ml 로조절하여마취를유지하였다. S군은 sevoflurane 의호기말농도를 1.5-2.0% 로, remifentanil 의효과처농도를 1-3 ng/ml로마취를유지하였다. 피부봉합이끝나는시점에서모든약제의사용을중단하고, 100% 산소 5 L/min 으로환기를하며마취를종료하였다. 자발호흡을회복시킨후 glycopyrrolate 0.4 mg 과 pyridostigmine (PyrinolTM, Myungmoon, Korea) 10 mg 을정주해근이완을역전시키고발관하여환자를회복실로이송하였다. 마취유도 2분전과삽관직전, 삽관직후, 피부절개직전, 피부절개직후, 발관직전, 회복실에서각각의평균동맥압, 심박수, BIS 수치를기록하였다. 마취에서회복속도를측정하기위해수술종료시점에서마취약제의사용중단후자발적으로눈을뜨는시간 (time to eye opening), 발관까지걸리는시간 (time to extubation), 이름을말할수있는시간 (time to stating name) 을기록하였 다. 또한마취에서회복하는과정과회복실에있는동안오심, 구토의발생, 기침발생, 무호흡발생여부, 통증정도를관찰하여기록하였다. 회복실에서오심과구토의증상이있는경우 ramosetron (Nasea TM, Astellas, Japan) 0.3 mg 으로치료하였고, 통증을호소한경우는 ketorolac (KerominTM, Hana, Korea) 을정맥투여하였다. 통계학적분석은 SPSS (version 18.0) 통계프로그램을사용하였다. 측정한자료는평균 ± 표준편차로표시하였으며군내및군간평균동맥압과심박수, BIS 수치는 repeated measured ANOVA 로하였으며, 각성시간의비교는 t-test 를, 합병증의발생빈도는 chi-square test 를이용하여분석하였다. P 값이 0.05 미만인경우통계학적으로유의하다고판정하였다. 결과 마취유도 2분전, 삽관직전과직후, 수술시작전과후, 발관직전과회복실에서의평균동맥압과심박수는두군간비교에서유의한차이가없었다 (Fig. 1, 2). BIS Fig. 1. Perioperative changes of mean arterial pressure (MAP). T0, 2 minutes before the induction; T1, right before the endotracheal intubation; T2, right after the endotracheal intubation; T3, right before the beginning of operation; T4, right after the beginning of operation; T5, right before the extubation; T6, postanesthetic care unit (PACU). Group P, propofol and remifentanil; Group S, sevoflurane and remifentanil. Each data was shown as mean ± SD (between groups: P = 0.465). 139
Fig. 2. Perioperative changes of heart rate (HR). T0, 2 minutes before the induction; T1, right before the endotracheal intubation; T2, right after the endotracheal intubation; T3, right before the beginning of operation; T4, right after the beginning of operation; T5, right before the extubation; T6, postanesthetic care unit (PACU). Group P, propofol and remifentanil; Group S, sevoflurane and remifentanil. Each data was shown as mean ± SD (between groups: P = 0.691). Fig. 3. Perioperative change of bispectral (BIS) index. T0, 2 minutes before the induction; T1, right before the endotracheal intubation; T2, right after the endotracheal intubation; T3, right before the beginning of operation; T4, right after the beginning of operation; T5, right before the extubation. Group P, propofol and remifentanil; Group S, sevoflurane and remifentanil. Each data was shown as mean ± SD (between groups: P = 0.001). Table 2. Emergence times from discontinuance of anesthetic drug Group P (n = 40) Group S (n = 40) Time to eye opening (min) 11.2 ± 2.7 10.4 ± 1.9 Time to extubation (min) 11.9 ± 2.4 11.1 ± 1.9 Time to stating name (min) 14.1 ± 2.2 14.5 ± 2.4 Each data was shown as mean ± SD. Group P, propofol and remifentanil; Group S, sevoflurane and remifentanil. There were no differences between two groups. 수치는 P군에서 S군에비해유의하게낮았다 (P < 0.05) (Fig. 3). 수술이종료되는시점에서약제사용을중단한후자발적으로눈을뜨는시간, 발관까지걸리는시간, 이름을말할수있는시간은두군간에통계적으로유의한차이가없었다 (Table 2). 회복시발생된부작용은 Table 3에기술되어있다. 각성시기침은 P군에서는없었고, S군에서는 4건있었다. 회복실에서오심만발생한경우는 P군에서 3건, S군에서 10건으로통계적으로유의한차이가있었다 (P < 0.05). 오심과구토모두를보인경우는 P군에서는없었고 S군에서 3건있었다. 무호흡이발생한경우는두군모두에서없었고, 떨림증상은 P군에서 1건발생하였다. 통증을 Table 3. Emergence complications of postoperative period Group P (n = 40) Group S (n = 40) Coughing 0 (0%) 4 (10%) Nausea and Vomiting 3 (7.5%) 13 (32.5%)* Nausea only 3 (7.5%) 10 (25%)* Nausea with vomiting 0 (0%) 3 (7.5%) Breath holding 0 (0%) 0 (0%) Shivering 1 (2.5%) 0 (0%) Number (%). Group P, propofol and remifentanil; Group S, sevoflurane and remifentanil. *P < 0.05. 호소한경우는 P 군에서만 2 건있었다. 140
A Comparison of the Recovery Characteristics between Propofol-remifentil and Sevoflurane-remifentail Anesthesia for Total Thyroidectomy 고찰 흡입마취제인 sevoflurane 은혈액-가스용해도가낮기때문에술중마취심도를환자의혈역학적인상황에맞게조절하기용이하고, 마취에서의회복도빠르다. Propofol 을이용한전정맥마취는전통적인흡입마취제를이용한마취에비해빠르고부드러운마취회복과마취후부작용발생빈도의감소와, 마취가스로인한수술장내공기오염을최소화한다는장점을갖는다. Sevoflurane 과 propofol 에대한각성시간에관한연구는수술의종류와시간, 약제중단시점과방법, 아편유사제의사용여부나종류, N 2O 의사용여부에따라서다양한결과를보이고있다. Fredmann 등은 10 sevoflurane 과 propofol을 60% N 2O와 fentanyl 을함께사용해서마취를유지했을때각성시간에있어서는차이가나지않는다고하였다. Lien 등도 11 sevoflurane과 propofol을 60-70% N 2O를사용하며보충적으로 fentanyl 을사용한결과눈을뜨는시간이 9분과 8분으로차이가없었고, 발관시간도 9.1 분과 8.6 분으로차이가나지않는다고하였다. 본연구에서는 N 2O를사용하지않고아편유사제는 remifentanil 을선택하였지만, propofol 과 sevoflurane 을이용한두군에서각성시간에차이가나지않아위의연구들과유사한결과를보여주었다. 그러나 Wandel 등은 12 외래환자마취에서 sevoflurane 으로마취한군이 propofol 로마취한군에비해, 구두명령에반응하여눈을뜨는시간 (7.2 분 vs. 12.6 분 ), 구두명령에손을쥘수있는시간 (8.2분 vs 13.8분 ), 발관시간 (6.6분 vs. 9.8분 ) 이더짧았다고보고하였다. 이와반대로 Larsan 등은 13 propofol 과 remifentanil 을이용해마취를한경우가흡입마취제인 sevoflurane 이나 desflurane 을 N 2O와같이사용해마취를한경우보다더빠른각성을보인다고했다. 이런다양한연구결과는전술한대로여러가지조건들이일치하지않기때문으로생각된다. 폐포내흡입가스의제거는신선가스의유량에따라달라질수있는데, 본연구의 sevoflurane 을사용한군에서 5 L를초과하는신선가스유량을공급하면서회복시켰다면 propofol 을이 용한군보다더빠른회복시간이나타났을가능성이있다. 수술후회복실에서나타난부작용중에서기침, 구토, 통증, 떨림의증상은두군에서차이가없었다. 오심은 sevoflurane 을사용한군이 propofol 을사용한군에비해유의하게높게나타났다. Propofol 을이용해전정맥마취를할경우기존의흡입마취제로마취를한경우와비교해서 PONV 가적게나타난다고한다. 14-18 Nelskyla 등은 14 부인과소수술에서 propofol 을이용해마취를한군에서 PONV 가 5% 에서발생한데비해 sevoflurane 을이용한군에서 64% 에서발생했기때문에 PONV 의측면에서 propofol 을이용하는것이더좋다고하였다. Raeder 등은 15 당일수술을위한마취에서회복속도는 sevoflurane 을사용한군이 propofol 을사용한군에비해더빨랐지만, PONV 가더많이발생했다고하였다. Sevoflurane 뿐만아니라 desflurane 16 이나 isoflurane, 17 enflurane 18 을사용한경우도 propofol 을이용한군과비교해서 PONV 의빈도가더높으며, N 2O역시여러연구에서 19,20 PONV 의발생빈도를증가시킨다고하였다. Propofol 이흡입마취제와비교해서오심과구토를낮추는효과의기전은명확히밝혀지지는않았지만, 5-HT3 수용체를차단하거나중추신경계의화학수용체방아쇠영역과오심및구토와관련된미주신경등을직접억제해 21 생기는것으로이해되고있다. 본연구에서 sevoflurane 을마취유지에이용한군에서도 propofol을마취유도제로사용하였는데, propofol과 thiopental sodium 을마취유도제로사용하고 PONV 를비교한연구에서 propofol 을이용한경우 28-50% PONV 감소효과가있다고보고하였다. 22,23 그러나 Gan 등은 24 유방절제술을받은환자에서 propofol 을마취유도제로사용하여도 PONV 의감소효과는없었다고하였다. 1시간이상의수술에서 propofol 의항구토효과를기대하기위해선지속주입이필요하다고하였으므로 25 본연구에서는두군모두에서수술시간이 2시간내외였기때문에마취유도제로사용한 propofol 은 PONV 의발생에영향을주지못하였을것으로생각된다. 수술시사용된아편유사제도 PONV 에영향을줄수 141
있는중요한요인이다. 아편유사제는뇌간 (brain stem) 의화학수용체유발영역 (chemoreceptor trigger zone) 에대한직접적인작용, 운동유발성오심에대한전정기관 (vestibular organ) 의감작 (sensibilization), 위장관분비의증가, 위운동성지연, 위배출지연등의기전으로오심 구토를유발한다고한다. 26 본연구에서사용한 remifentanil 은혈장및조직의 esterase 에의해가수분해되어발현시간이빠르고작용시간이짧으며축적작용이거의없다. 27 Dershwitz 등은 28 remifentanil이나 alfentanil 과같은단기작용아편유사제는 PONV 의큰위험요소로작용하지않는다고하였다. 기존의연구들에서는 3,4 갑상선절제술시 PONV 는 60-64% 까지도발생하는것으로보고되어왔으나, 본연구에서는전반적으로 PONV 의발생빈도가낮게나타났다. 이는연구대상자중에서 PONV 의위험인자인비만, 멀미, 과거오심 구토기왕력이있는환자를제외하였고, N 2O를사용하지않고, 단기작용아편유사제인 remifentanil을사용했기때문으로생각된다. 본연구에서는 PONV 의발생을회복실에서만관찰해서 propofol 과 sevoflurane 의 PONV 에대한장기적인영향은평가하지못한제한점이있다. Tramer 등에 29 의하면 84개의 PONV 에관한논문에서 6,069명의환자를분석한결과 propofol 을마취유지를위해사용했을때술후초기에만 (0-6 h) 오심과구토를억제하는효과를보이며, 그이후에는임상적중요성이떨어진다고하였다. 하지만갑상선절제술의경우초기에혈종이생기면창상치유에문제를유발할수있기때문에술후초기에오심과구토를억제하는것이의미가있다고생각한다. 이상의결과로볼때성인의갑상선절제술에서 sevoflurane 을이용해마취를유지한경우와 propofol 을이용해마취유지를하는경우모두술중마취유지나마취회복속도에는차이가없었으나, 술후오심의발생빈도는 propofol 을이용한경우가낮았다. 따라서수술부위의창상회복을고려해볼때 propofol 을이용하는것이더유익할것으로생각된다. 참고문헌 1. Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer Statistics in Korea: Incidence, Mortality, Survival and Prevalence in 2010. Cancer Res Treat. 2013;45:1-14. 2. Joe HB, Park EJ, Park SK, Kim EJ, Park JH, Choi JW, et al. The effects of prophylactic dolasetron and induction with propofol on postoperative nausea and vomiting after thyroidectomy. Korean J Anesthesiol 2009;57:320-6. 3. Wang JJ, Ho ST, Lee SC, Liu YC, Liu YH, Liao YC. The prophylactic effect of dexamethasone on postoperative nausea and vomiting in women undergoing thyroidectomy: a comparison of droperidol with saline. Anesth Analg 1999;89:200-3. 4. Fujii Y, Saitoh Y, Tanaka H, Toyooka H. Prophylactic antiemetic therapy with granisetron in women undergoing thyroidectomy. Br J Anaesth 1998;81:526-8. 5. Golembiewski J, Chernin E, Chopra T. Prevention and treatment of postoperative nausea and vomiting. Am J Health Syst Pharm 2005;62:1247-60. 6. Edmond I Eger II. Inhaled anesthetics: uptake and distribution. In: Miller RD, editors. Miller s anaesthesia. 7th ed. Philadelpia, Elsevier, 2010, p 540-2. 7. TerRiet MF, DeSouza GJA, Jacobs JS, Young D, Lewis MC, Herrington C, et al. Which is most pungent: isoflurane, sevoflurane or desflurane? Br J Anaesth 2000;85:305-7. 8. Jeong JH, Song SO, Kim HD. A comparison of the recovery characteristics of propofol and sevoflurane anesthesia under bispectral index system monitoring. Korean J Anesthesiol 2004;46:528-34. 9. Sneyd JR, Carr A, Byrom WD, Bilski AJ. A meta-analysis of nausea and vomiting following maintenance of anaesthesia with propofol or inhalational agents. Eur J Anaesthesiol 1998;15:433-45. 10. Fredman B, Nathanson MH, Smith I, Wang J, Klein K, White PF. Sevoflurane for outpatient anesthesia: a comparison with propofol. Anesth Analg 1995;81:823-8. 11. Lien CA, Hemmings HC, Belmont MR, Abalos A, Hollmann C, Kelly RE. A comparison: the efficacy of sevoflurane-nitrous oxide or propofol-nitrous oxide for the induction and maintenance of general anesthesia. J Clin Anesth 1996;8:639-43. 12. Wandel C, Neff A, Böhrer H, Browne A, Motsch J, Martin E. Recovery characteristics following anaesthesia with sevoflurane or propofol in adults undergoing out-patient surgery. 142
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