Anesth Pain Med 2007; 2: 219~223 임상연구 성인개심술마취유도제로사용한 Remifentanil 의혈역학적효과 울산대학교의과대학서울아산병원마취통증의학교실 이윤경ㆍ최인철ㆍ심지연ㆍ함경돈ㆍ김영국ㆍ도경준ㆍ김진석 The Hemodynamic Effects of Remifentanil as an Induction Agent in Cardiac Surgery with improper ventilation. (Anesth Pain Med 2007; 2: 219 223) Key Words: cardiac, induction, remifentanil. Yoon Kyung Lee, M.D., In Cheol Choi, M.D., Ji Yeon Sim, M.D., Kyung Don Hahm, M.D., Young Kug Kim, M.D., Kyoung Jun Do, M.D., and Jin Seok Kim, M.D., Department of Anesthesiology and Pain Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea Background: Remifentanil may be advantageous during induction of anesthesia in patient with heart disease because of rapid onset and hemodynamic stability. Some study reported that remifentanil showed complications such as profound bradycardia, severe hypotension and rigidity. The purpose of this study is to investigate the hemodynamic changes and side effects of remifentanil by using the methods of bolus administration during induction of anesthesia in cardiac surgery. Methods: Fifty eight patients of ASA physical status 2~3 undergoing cardiac surgery were enrolled into 3 groups. We administered no remifentanil in Group A, 5μg/kg of remifentanil in Group B and 10μg/kg of remifentanil in Group C. After bolus administration of remifentanil over 30 sec, we infused 0.2μg/kg/min of remifentanil continuously. All group received continuous infusion of 100μg/ kg/min of propofol. After loss of consciousness, 0.15 mg/kg of vecuronium was administered. After the Bispectral index (BIS) value became lower than 60, intubation was done. Mean arterial pressure, heart rate, the incidence of cough, jaw and chest wall rigidity, and BIS value were measured initially and 1, 2, 3, 4, 5 minutes before intubation and 1, 2, 3, 4, 5 minutes after intubation. Results: Mean arterial pressures of group B and C were significantly lower than those of group A (P < 0.05). Heart rate was similar among the groups. Group C showed a greater incidence of jaw rigidity (77%) compared with group A (35%) and group B (35%) (P < 0.05). The incidence of chest wall rigidity (66%) in group C was greater than group A (5%) and group B (15%) (P < 0.05). Conclusions: Remifentanil used as an induction agent (5μg/kg or 10μg/kg) may cause hypotension and jaw, chest wall rigidity 논문접수일 :2007 년 8 월 17 일책임저자 : 최인철, 서울시송파구풍납 2 동 388-1 울산대학교의과대학서울아산병원마취통증의학과우편번호 : 138-736 Tel: 02-3010-3862, Fax: 02-470-1363 E-mail: icchoi@amc.seoul.kr 219 서 마취유도와기관내삽관시교감신경계자극에의한혈압과심박수증가, 혈중카테콜아민농도상승으로심근허혈, 좌심실부전, 부정맥, 뇌출혈등의위험성이증가한다. 1,2) 따라서심장질환이있는환자의마취는심안정성과혈역학적반응둔화를위하여 fentanyl, alfentanil 등의아편양제재를사용한다. 3,4) 그러나아편양제재는단시간과량주입하거나장기간투여한경우호흡억제가지속될수있으며술후신경학적검사등의필요로인해빠른회복이필요한경우문제가될수있다. Remifentanil은 μ-아편양제수용체에작용하며진통작용발현시간이매우빠르고비특이적 esterase에의해분해되어축적작용이없어작용시간이짧다. 간이나신기능에이상이있는환자에서도제거율에변화가없으므로작용이연장되지않는다. 5) 건강한성인에서혈역학적안정을위해마취유도보조제로 4μg/kg를일회정주하여사용할수있고, 6,7) 또한심장질환이있는환자에서균형마취방식으로지속정주하여사용할수있다. 8) 마취유도제로서의 remifentanil의정주는여러가지논란이있는데 DeSouza 등에 9) 의하면 remifentanil 1μg/kg를일회정주하고 0.1μg/kg/min를지속투여한후 2-3분뒤에분당 30회의심한서맥과수축기혈압이 70 mmhg의저혈압을나타내었고 Wang 등에 10) 의하면 remifentanil 0.5μg/kg를일회정주하고 0.025 μg/kg/min를지속투여한후 2 분뒤에심한서맥과저혈압을나타내었다고한다. 반면 Hall 등에의하면 11) remifentanil 0.5μg/ kg를일회정주하고 0.25μg/kg/min로지속투여한후 3분뒤에삽관한경우분당 60회이하의서맥이나수축기혈압 90 mmhg이하의저혈압은발생하지않았다고보고하였다. 그러나이들보고에서의서맥과저혈압의발생은술전에 β- 차단제나 morphine을투여하거나 etomidate를마취유도제로함께사용하고 9) 3 vol% 이상의 sevoflurane을함께사용하는등 10) 마취유도방법의차이에기인하는것으로생각되어본연구는개심술환자들을대상으로술전아편양제재와마취중흡입마 론
220 Anesth Pain Med Vol. 2, No. 4, 2007 취제사용을배제하고, remifentanil이주된마취제로사용되는 remifentanil-propofol균형마취에서 remifentanil이야기하는혈역학적변화정도와부작용을살펴보고자하였다. 대상및방법전신마취하에개심술을받는미국마취과학회신체등급분류 II 또는 III에해당하는 35-74세의성인심장질환자 58명을대상으로하였다. 병원윤리위원회의승인을받은후마취전방문시에환자에게연구목적과방법에대한설명을시행하고서면동의를받았다. 상기도감염, 후두나기관부위의수술을받았던병력이있는환자, 천식이나만성폐쇄성폐질환이있거나기관지확장제를투여받는환자, 기도유지가어려울것으로예상되는환자들은대상에서제외하였다. 모든환자는수술전날자정부터금식하였으며마취전투약은수술 30분전 midazolam 7.5 mg (Dormicom R, Roche Korea, Korea) 을경구투여하거나수술실입실후침습적동맥혈압, 심전도, 맥박산소포화도, Bispectral index (BIS) 감시하에환자감시장치하에 midazolam 2 mg을정맥주사하였다. 항콜린성전투약제는삽관환경과혈역학적변수에영향을줄수있어투여하지않았다. 술전수액투여는환자의금식시간에따라보충하였다. 마취유도는 100% 산소투여하에 propofol (Fresofol R 2%, Fresenius Kabi, Korea) 을 100μg/kg/min로지속정주하였고환자는무작위로 3개군으로나누어서 A군 (n = 20) 은 remifentanil (Ultiva R, GlaxoSmithKline, UK) 을일회정주하지않았고, B군 (n = 20) 은 remifentanil 5μg/kg를일회정주하였고, C군 (n = 18) 은 remifentanil 10μg/kg를일회정주하였다. Remifentanil의투여는지속주입기 (AS40A R, Baxter healthcare corp, USA) 를이용하여일회주입모드에서 30초동안시행되었고이후 0.2μg/kg/min로지속정주하였으며이중맹검법으로삽관을시행할마취의가각군별용량을알수없게하였다. 환자의의식이소실되면 vecuronium 0.15 mg/kg를투여하였고 remifentanil 주입 5분후모든환자에서 BIS가 60 이하인것을확인하고기관내삽관하였다. 기관내삽관은 3년이상의경험을가진숙련된마취의가실시하였고, 남자환자들에서는내경 8.0 mm, 여자환자들에서는내경 7.5 mm를사용하였으며, 1회시행하여실패한경우나 30 초이내에시행되지않는경우는연구에서제외하였다. 삽관후에는마취유도시와동일한유량의신선가스로호기말이산화탄소농도가 30-35 mmhg가되도록조절호흡을시행하였고다른자극이없도록하였다. 평균동맥압이 60 mmhg 이하로감소하면 ephedrine 5 mg을정주하고분당 45회이하의서맥이발생하면 atropine 0.5 mg을정주하였으며저혈압과서맥이약물에반응하지않는경우에는 remifentanil의주입을중단하였다. 대상환자에대하여마취유도전 (Baseline, B), remifentanil주입후 5분간매 1분마다 (R-1, R-2, R-3, R-4, R-5), 그리고기도 삽관 (intubation, I) 과그후 5 분간매 1 분마다 (I-1, I-2, I-3, I-4, I-5) 의평균동맥압, 심박수, BIS값을측정하였고, 모든수치는평균 ± 표준편차로표시하였다. 저혈압과서맥이외에발생가능한부작용으로악관절과흉부근강직, 그리고기침의발생을관찰하였고악관절과흉부근강직은마스크환기가가능한지여부를측정하였다. 각군간의비교를위해 two-way repeated measures of analysis of variance (ANOVA) 를시행하였고, P < 0.05 인경우를통계적으로유의한것으로판정하였다. 결 평균동맥압은 remifentanil주입 2분후까지는각군간에차이가없었고주입 3분후부터기관내삽관까지는 A군에비하여 B와 C군이유의한감소를보였으나 (P < 0.05) B군과 C군사이에는의미있는차이를보이지않았다 (Fig. 1). 기관내삽관시와삽관후 1분에서 C군은 A와 B군에비해의미있는감소를보였으며삽관 2 분후부터는각군간의차이가없었다 (Fig. 1). 마취유도전의혈압을기준으로 30% 이상감소한심한저혈압은 A군의경우환자의 45% 에서나타났으며 B군은 75%, C군은 100% 에서각각발생하여 B, C군에서저혈압발생의정도와빈도가높은것으로나타났다 (Table 1). 심박수의변화는각군간에의미있는차이를보이지않았다 (Fig. 2). 분당심박수가 45회이하로떨어지는심한서맥의발생도 A군 15%, B군 10% 그리고 C군에서 17% 로차이를보이지않았고, 세군모두에서기관내삽관후의빈맥은나타나지 Fig. 1. The changes of mean blood pressure. *: P < 0.05 compared to group A, : P < 0.05 compared to group B. Values are presented as mean ± SD. R: remifentanil administration, R-1: one minutes after remifentanil administration, R-2: one minutes after remifentanil administration, R-3: one minutes after remifentanil administration, R-4: one minutes after remifentanil administration, R-5: one minutes after remifentanil administration, I: intubation. I-1: one minutes after intubation, I-2: one minutes after intubation, I-2: one minutes after intubation, I-3: one minutes after intubation, I-4: one minutes after intubation, I-5: one minutes after intubation. 과
이윤경외 6 인 : 성인개심술마취유도에서 Remifentanil 사용 221 Table 1. Severity of Hemodynamic Changes Blood pressure Heart rate Remifentanil < 10% of 10-30% of > 30% of Initial BP Initial BP Initial BP > 60 bpm 45-60 bpm < 45 bpm Group A (n = 20) 2 (10%) 9 (45%) 9 (45%) 4 (20%) 13 (65%) 3 (15%) Group B (n = 20) 0 5 (25%) 15 (75%)* 8 (40%) 10 (50%) 2 (10%) Group C (n = 18) 0 0 18 (100%)* 4 (22%) 11 (61%) 3 (17%) Values are presented as numbers. *: P < 0.05 compared with group A, BP: blood pressure, bpm: beat per minute. Table 2. Severity of Side Effects Jaw rigidity Chest wall rigidity Cough Remifentanil Ventilation Ventilation No No No Once Twise Proper Improper Proper Improper Group A (n = 20) 13 (65%) 6 (30%) 1 (5%) 19 (95%) 0 1 (5%) 20 (100%) 0 0 Group B (n = 20) 13 (65%) 2 (10%) 5 (25%) 17 (85%) 2 (10%) 1 (5%) 13 (65%) 1 (5%) 6 (30%)* Group C (n = 18) 4 (22%) 6 (33%) 8 (44%)* 6 (33 %) 6 (33%) 6 (33%)* 12 (67%) 1 (6%) 5 (28%)* Values are presented as %. *: P < 0.05 compared with group A, : P < 0.05 compared with group B. Fig. 2. The changes of heart rate. No significant differences between groups. Values are presented as mean ± SD. R: remifentanil administration, R-1: one minutes after remifentanil administration, R-2: one minutes after remifentanil administration, R-3: one minutes after remifentanil administration, R-4: one minutes after remifentanil administration, R-5: one minutes after remifentanil administration, I: intubation, I-1: one minutes after intubation, I-2: one minutes after intubation, I-2: one minutes after intubation, I-3: one minutes after intubation, I-4: one minutes after intubation, I-5: one minutes after intubation. 않았다 (Table 1). 승압제투여량은 A군에비해 B군과 C군에서유의하게많았으며, remifentanil의투여중단빈도는 B군에서 4회, C군은 6회 Fig. 3. The total dose of vasopressor. *: P < 0.05 compared with group A. Values are presented as mean ± SD. 로 remifentanil의투여를중단하지않았던 A군에비해유의하게많았다 (P < 0.05, Fig. 3). 악관절과흉부근강직의빈도는 A군과 B군에비하여 C군에서많이발생했으며일시적인환기장애발생빈도도높게나타났으나 (Table 2) 악관절과흉부근강직으로인해산소포화도가떨어진환자는없었다. 기침은 A군에비해 B군과 C군에서발생빈도가높았다 (Table 2). BIS 수치는 remifentanil투여 3, 4, 5 분후에 A군에비해 B군
222 Anesth Pain Med Vol. 2, No. 4, 2007 Fig. 4. The changes of BIS value. *: P < 0.05 compared to group A. Values are presented as mean ± SD. R: remifentanil administration, R-1: one minutes after remifentanil administration, R-2: one minutes after remifentanil administration, R-3: one minutes after remifentanil administration, R-4: one minutes after remifentanil administration, R-5: one minutes after remifentanil administration, I: intubation, I-1: one minutes after intubation, I-2: one minutes after intubation, I-2: one minutes after intubation, I-3: one minutes after intubation, I-4: one minutes after intubation, I-5: one minutes after intubation. 과 C군에서유의하게낮았고, 기관내삽관 1분후에 A군에비해 C군에서유의하게낮았다 (Fig. 4). 고 마취유도와기관내삽관은혈압과심박수의변화, 그리고심박출량의장애를야기할수있다. 심장질환을가지고있는환자에서는마취전후로혈역학적안정성을유지하는것이마취유도의목표라고할수있다. 기관내삽관시의유해반응을억제하기위해베타아드레날린차단제, 칼슘수용체차단제, 혈관확장제, 국소마취제, 아편양제재등의약제를보조적으로투여하는방법들이연구되어왔고다양한정도의효용성이보고되었다. 12) 전통적으로심장질환이있는환자의마취유도는중등도내지고농도의아편양제재를사용하여혈역학적안정성을유지하였으나고용량투여및주입시간에따라술후지속적인호흡억제를일으킬수있는단점이있다. 13) Remifentanil은장시간주입해도투여중지후의회복이빠른아편양제재로지속정주의방법으로사용할때혈역학적안정성을유지할수있기때문에심장질환이있는환자에서균형마취의일부로사용되고있다. 14) 그러나 remifentanil의일회정주방법은심한저혈압과서맥이발생할수있으므로특히심장질환을가진환자에서더욱주의를요한다. 9,10) Egan 등은 15) 심장질환이있는 8명의환자에서 remifentanil 0.2μg/kg을일회정주한후 4명에서심한서맥, 저혈압, 심전도상 ST 분절하강을보였고심박출량이저하되었다고하였다. Altermatt와 Munoz remifentanil 0.5μg/kg/min와 propofol 2μg/ml의목표농도 는 16) 찰 주입법으로마취유도한환자에서 2회의무수축발생을보고하였으나두차례모두기관내삽관을시도할때발생하여삽관조작에따른무수축을배제할수는없다. 양측미주신경섬유절제술을받은개에서 fentanyl로인한서맥이효과적으로억제된것으로보아아편양제재사용으로인한저혈압과서맥은미주신경과관련되어있는것으로생각된다. 17) 본연구에서는서맥의빈도는높지않았으나 Mcneil 등에의하면 7) remifentanil 4μg/kg와 propofol 2mg/kg를일회정주한후분당 45회의심한서맥이발생하였다고한다. Reyntjens 등 은 18) 심장질환이있는소아들을대상으로한연구에서 remifentanil 투여와동시에항콜린제인 glycopyrrolate를 6μg/kg 정주하였고마취전심박수와차이를보이지않아 glycopyrrolate의전처치가유용하다고하였다. Joo 등에의하면 19) glycopyrrolate 0.2 mg을전처치한후 5μg/kg의 remifentanil을일회정주하여서맥과저혈압의빈도를높이지않고안정적인기관내삽관과마취유도가가능하였다고하였다. 반면 Glass 등과 5) Hall 등은 11) remifentanil 일회정주전에 glycopyrrolate를사용하여빈맥이발생하였다고하였다. 따라서서맥을조절하기위해항콜린제를사용할때에는 remifentanil과동시에투여하거나서맥발생후투여하는것이빈맥발생을줄일수있을것으로생각된다. 아편양제재에의한근육강직현상은환기장애를초래할수있어아편양제재를이용한마취유도시기도삽관이되지않은환자에대하여특별한주의가필요하다. 근육강직의빈도는투여용량과투여속도, 아산화질소의사용여부, 근이완제의전투여, 환자의나이등에영향을받는것으로알려져있고, 20) 아편양제재에의한근육강직에대한연구들에따르면다량을급속정주하는경우근육강직의빈도가높은것으로나타났다. 21,22) 본연구에서도 10μg/kg의 remifentanil 정주후악관절과흉부근강직의빈도가높았고, 그로인한환기장애의발생도많았다. 그러나강직현상은일시적으로나타났고산소포화도가 95% 이하로감소한환자는없었으며 propofol과 vecuronium을함께사용하였기때문으로생각된다. Stevens와 Wheatley의 23) 연구와같이 remifentanil의정주속도를 90초이상으로느리게하고의식소실의정도를감시하여의식소실과동시에근이완제를사용하는것이 remifentanil로인한근육강직을예방하는좋은방법이다. Propofol과야편양제재를병용투여하는경우두약제의상호작용에대하여많은연구가진행되었으나아직논란의여지가많다. 대부분의아편양제재는 propofol의진정효과를크게하고요구량을감소시키는것으로알려져있고, 특히 remifentanil은다른아편양제재에비해장점이있다고알려져있다. 24,25) 본연구에서도 BIS의수치가 10μg/kg의 remifentanil 정주시더빨리감소한것을볼수있었다. Propofol과 remifentanil의용량반응관계가아직확실히밝혀지지는않았으나기존에환자가복용하던약물과마취전투약이나마취유도시병용하는다른마취제, 환자의상태등을고려하여신중히사용하여야한다.
이윤경외 6 인 : 성인개심술마취유도에서 Remifentanil 사용 223 본연구에서와같이일회정주없이 remifentanil 0.2μg/kg/ min의지속정주만으로도마취유도를위한적절한심도의마취가되었으나 BIS수치는 5분이후에 60 이하로떨어졌으므로 BIS감시를하지않는경우 5분이상의충분한시간이지난후에기관내삽관을시행하여야환자의예기치않은각성을방지할수있을것으로생각된다. 그러나빠른마취유도가필요할경우항콜린제나승압제를병용하면서고용량의 remifentanil 을천천히정주하고 BIS수치를감시하여의식소실여부를파악하고기관내삽관을하여야할것으로사료된다. 결론적으로 remifentanil을주된마취유도제로사용하는경우 5μg/kg나 10μg/kg을일회정주하면일회정주하지않은군에비해저혈압의발생빈도가높고, 환기가되지않는근육강직의발생이올수있다. 따라서, 심장질환이있는환자의마취유도는 remifentanil의일회정주보다는서서히지속주입을하는방법이좋을것으로생각된다. 참고문헌 1. Edwards ND, Alford AM, Dobson PM, Peacock JE, Reilly CS: Myocardial ischaemia during tracheal intubation and extubation. Br J Anaesth 1994; 73: 537-9. 2. Fox EJ, Sklar GS, Hill CH, Villanueva R, King BD: Complications related to the pressor response to endotracheal intubation. Anesthesiology 1977; 47: 524-5. 3. Collard E, Delire V, Mayne A, Jamart J, Louagie Y, Gonzalez M, et al: Propofol-alfentanil versus fentanyl-midazolam in coronary artery surgery. J Cardiothorac Vasc Anesth 1996; 10: 869-76. 4. 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