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1 Anesth Pain Med 2010; 5: 255~259 임상연구 소아부안검교정술에서수술전정주한 Acetaminophen 이술후각성섬망에미치는영향 동아대학교부속병원마취통증의학과 임연희ㆍ진영준ㆍ정찬종ㆍ최소론ㆍ이원지 Effects of acetaminophen on postoperative emergence delirium in children undergoing epiblepharon correction Pain Med 2010; 5: ) Key Words: Acetaminophen, Pediatric anesthesia, Postoperative delirium. Youn Hee Lim, Young-Jhoon Chin, Chan Jong Chung, So Ron Choi, and Won-Ji Rhee 서 론 Department of Anesthesiology and Pain Medicine, Dong-A University Hospital, Busan, Korea Background: Emergence delirium is a common problem after general anesthesia in children. Postoperative pain control reduces the incidence of emergence delirium. Opioids and NSAIDs have been successfully used to inhibit intraoperative and postoperative pain. Instead of them, acetaminophen is used to reduce side effects of opioids and NSAIDs. This study evaluated the effect of acetaminophen on emergence delirium after general anesthesia in children undergoing a epiblepharon correction. Methods: Sixty children, aged 1 10 years (ASA physical status I, II) undergoing epiblepharon correction, were enrolled in this study. Acetaminophen (group A) received 15 mg/kg of acetaminophen, control group (group C) received 1.5 ml/kg of normal saline. Anesthesia was induced with 2.0 mg/kg of ketamine and maintained by vol% sevoflurane with N 2O 1.5 L/min O L/min. The delirium score was recorded at 10 minutes after arrival at recovery room by an independent observer using the four point scale of Aono. Results: There were no significant differences between the two groups regarding the time to extubation and discharge from the recovery room. The incidence of emergence delirium was 23% in group A and 32% in group C, but this did not have statistical significance. The incidence of vomiting was similar in both group. Conclusions: Preoperative intravenous acetaminophen of 15 mg/kg application does not reduce the incidence of postoperative delirium in children undergoing epiblepharon correction. (Anesth Received: March 15, Revised: March 26, Accepted: April 9, Corresponding author: Young-Jhoon Chin, M.D., Department of Anesthesiology and Pain Medicine, Dong-A University Hospital, 1, Dongdaesin-dong 3-ga, Seo-gu, Busan , Korea. Tel: , Fax: , yjjin@dau.ac.kr 소아환자는전신마취로부터각성시안절부절하고짜증을부리고우는등흥분 (agitation) 이나섬망 (delirium) 상태를일으킬수있으며, 이는신체손상을야기하거나감시장치의작동을어렵게만들어회복실에서의관리를어렵게만들수있으며, 회복실에서머무는시간을연장시키거나, 환자의보호자혹은다른환자들에게불안감을야기시킬수있으며, 게다가수술부위의손상을일으킬수있는문제점이있다. 각성섬망을일으키는인자에대한연구들이많이이루어지고있으나명확한원인은밝혀지지않았다. 주된원인으로는술전감정상태, 연령, 낯선환경, 대사장애, 신경장애, 약물, 저산소증특히술후통증이각성섬망의주요원인으로생각되고있다 [1]. 따라서각성섬망을예방하기위해수술전 opioids, NSAIDs의정주를많이사용하고있다. 하지만 opioids는호흡억제, 서맥, 오심, 구토, 그리고 NSAIDs는신기능손상이나위장관및수술부위출혈등의부작용을발생시키는경우가많아이들의사용을꺼리는경우가종종있다 [2]. Acetaminophen은이들이가지고있는부작용의빈도를줄이면서우수한진통효과를가지고있어 opioids나 NSAIDs 대신에많이사용되고있다. 편도절제술을받는어린이에서술전직장으로투여한 acetaminophen이술후진통효과를가진다는연구결과가있으며 [3], 동물실험에서 acetaminophen 은투여량에따라뇌전도상중추신경억제를가져오는것으로되어있으나 [4] 사람에서는약한진정을가져올수있다 [5,6]. 정주용 acetaminophen은경구용혹은직장용보다수술전후에사용하기편리한반면, propacetamol은분말형태의약을식염수나포도당용액에녹여사용해야하는불편 255

2 256 Anesth Pain Med Vol. 5, No. 3, 2010 함이있으며이에따른시간과인력이소비되고주사부위통증을야기하는단점이있다. 이에반해 acetaminophen은주사부위통증을야기하지않아마취전에사용하여도소아환자에게불편감을야기하지않는장점이있다 [7,8]. 이에본연구는부안검교정술을받는소아환자에서 acetaminophen의술전정주가술후각성섬망에미치는영향에대해알아보고자하였다. 대상및방법본연구는병원윤리위원회의승인후, 환자보호자에게마취와연구방법을설명하고동의를구한후시행하였다. 부안검교정술을받는소아환자중미국마취과학회신체등급분류제 1, 2급에해당하는 1 10세의건강한소아 60명을무작위로선택하였다. 대상환자중정신지체환자, 간질환자, 전신마취후흥분기왕력이있는환자는연구대상에서제외하였다. 환자는무작위로 acetaminophen (A군), control (C군) 의 2군으로나누었다. 수술전 4 6시간금식하였고, 마취전투약으로 glycopyrrolate (0.004 mg/kg) 만을투여하였다. 수술대기실에서소아의감정상태를 3단계 (1점, 조용한상태 ; 2점, 불안해하지만울지는않는상태 ; 3점, 매우불안해하며우는상태 ) 로나누어평가하였다. A군은정주용 acetaminophen 15 mg/kg, C군은 N/S 1.5 ml/kg을투여하였다. Ketamine 2.0 mg/kg을정주한후의식소실을확인후환아를보호자와격리하여수술실로이송하여. 수술실도착후 100% 산소를흡입시키면서마취시작전의심박수, 혈압을측정하였다. Rocuronium 0.6 mg/kg을정주한후근이완을확인하고기관내삽관을 실시하였고, N 2O 1.5 L/min O L/min을흡입하면서수술중활력징후에따라 sevoflurane을 vol% 로유지하고, 호기말이산화탄소분압을 mmhg가되도록호흡수를조절하였다. 심박수, 산소포화도, 호기말이산화탄소분압을지속적으로감시하였고, 혈압은 5분간격으로측정하였다. 수술종료후마취제사용을중단하고자발호흡과의식이돌아온후발관을하고자극을최소화하면서회복실로이송하였다. 회복실도착시, 도착후 10분의활력징후를측정한후마취에참여하지않은한명의동일한회복실간호사로하여금각성시감정과행동상태를 Aono 분류에따라 [9] 4단계 (1점, 조용한상태 ; 2점, 조용하지는않지만쉽게진정되는상태 ; 3점, 쉽게진정되지않고, 초조하고안절부절못하는상태 ; 4점, 호전적이고, 흥분되어있고, 방향감각이없는상태 ) 로나누어측정하게한후술후행동점수가 3 또는 4 점인경우를각성섬망으로간주하였다 (Table 1). 통계처리는 chi-square test와 T-test를이용하였고, P값이 0.05 미만인경우를유의성이있는것으로처리하였다. 결과 60명의환아를대상으로실험하였으며모두결과에포함되었다. 나이, 성별, 체중, 수술시간, 마취시간은두군간의차이가없었다 (Table 2). 수술전감정상태는두군간의통계학적인유의한차이가없었다 (Table 3). 수술중심박수와혈압의변화에있어서도두군간에유의한차이가없었다 (Fig. 1, 2). Table 1. Aono's Four Point Scale Calm 1 Not calm but could be easily calmed 2 Moderately agitated or restless 3 Combative, excited or disoriented 4 Behavioral scores 3 and 4 are considered as emergence delirium. Table 2. Demographic Data Table 3. Preoperative Emotional Status Calm 20 (67%) 15 (50%) Anxious 6 (20%) 8 (27%) Weeping 4 (13%) 7 (23%) Values are number (%) of patients. Group A: Acetaminophen group, Group C: Control group. Table 4. Postoperative Delirium Age (yr) 5.6 ± ± 3.1 Sex (M:F) 14:16 13:17 Weight (kg) 22.7 ± ± 11.4 Operation duration (min.) 48.7 ± ± 19.5 Anesthetic duration (min.) 72.0 ± ± 22.9 Values are mean ± SD or number of patients. Group A: Acetaminophen group, Group C: Control group. Yes 7 (23%) 10 (33%) No 23 (77%) 20 (67%) Values are number (%) of patients. Group A: Acetaminophen group, Group C: Control group. Yes: Aono's four point scale 3, 4 point, No: Aono's four point scale 1, 2 point.

3 임연희외 4 인 : 술전 acetaminophen 투여와소아각성섬망 257 Fig. 1. The changes of HR (heart rate) during anesthesia. There was no significant difference between two groups. Values are mean ± SD. Group A: Acetaminophen group, Group C: Control group. Induction: after induction, Preop: preoperation, Postop: postoperation, RR: on arrival at recovery room, RR 10 min.: 10 min. after arrival at recovery room. Fig. 2. The changes of MBP (mean blood pressure) during anesthesia. There was no significant difference between two groups. Values are mean ± SD. Group A: Acetaminophen group, Group C: Control group. Induction: after induction, Preop: preoperation, Postop: postoperation, RR: on arrival at recovery room, RR 10 min.: 10 min. after arrival at recovery room. Aono 분류에따라 1점 /2점/3점/4점의수는 A군에서는 13/10/6/1명이었으며, C군에서는 10/10/9/1명으로, 3점과 4점을각성시섬망으로간주하여 A군에서는 30명중 7명 (23%), C군에서는 30명중 10명 (33%) 에서각성섬망이발생하여 C 군에서상대적으로높은빈도수를보였으나통계적으로는유의한차이가없었다 (Table 4). 수술후부작용은두군에서오심과구토가각각 1명씩발생하였다. 고찰소아환자의마취관리에서부작용없이빠르고부드러운각성을얻기위해서많은연구들이시행되어져왔다. 각성섬망을감소시키는방법으로수술전 midazolam의경구투여, 통증조절을위한 NSAIDs 혹은 opioids의사용, 부위마취등이알려져있다 [10,11]. 이중에서 midazolam의사용은각성시흥분을줄이는데큰효과가없다는연구결과가있었으나 [12] 통증을조절하는약제들은효과가있다고보고되어있다. 수술중정주한 1.0 mg/kg의 ketorolac이각성섬망의빈도를감소시킨다고하였으며, 1 2μg/kg의 fentanyl로각성섬망이치료될수있다는결과도있었다 [13]. Ketorolac은비스테로이드성항염증성진통제로강력한진통작용을가지며호흡억제나진정효과등의부작용이없어 opioids에비해안전하게사용할수있지만수술후출혈이나신기능손상의위험성을가지고있다 [14,15]. Acetaminophen은 opioids나 NSAIDs가가지는부작용이없으며 15 mg/kg 이하의적정용량으로사용할경우에는간독성및다른부작용도없는것으로연구되어현재 opioids나 NSAIDs 를대신하여널리사용되고있다. Acetaminophen은조직의손상시 prostaglandin synthetase의작용을억제하여 arachidonic acid로부터 prostaglandin이생성되는과정을차단함으로써자율신경말단의감작을감소시킨다. 그리고또한중추신경의흥분을감소시켜진통작용을나타낸다 [3]. 이점을바탕으로술전에투여한 acetaminophen 의정주가술후의각성섬망을줄일수있을것이라고생각되었다. 하지만본연구에서전체환자 60명중각성섬망이나타난환자는 A군은 30명중 7명, C군에서는 30명중 10명으로 A군의빈도수는감소했으나통계학적으로유의한차이를보이지는않았다. 이러한결과가도출된것에는여러가지원인이기여했을수있는데우선부안검교정술자체의술후통증이크지않는수술이라는점이다. 편도적출술을받는환아를대상으로 ketorolac과 propacetamol을사용한연구에서대조군에비해우수한진통효과를나타내었다는보고가있으며 [16] 직장내투여한 acetaminophen 사용으로안전하고효과적인통증조절이가능하다는연구결과도있었다 [3]. 소아환자에서마취유도후 1μg/kg의 fentanyl을정주하여통증조절을할수있다고하며서혜부탈장수술을받은소아환자에서도호흡억제없이효과적인통증조절을할수있었다 [17]. 그러나이러한편도절제술이나서혜부탈장수술에비해부안검교정술은술후진통이비교적경미한수술이기때문에통증이각성섬망에미치는효과가적었을것이고, 따라서본연구에서술후통증조절의역할이각성섬망을감소시키는데크게기여하지못한것으로보인다. 또한마취유도제로사용한 ketamine의효과도실험결과

4 258 Anesth Pain Med Vol. 5, No. 3, 2010 에영향을미쳤을것으로생각된다. Ketamine은뇌의선택부위에서주로흥분성아미노산수용체인 NMDA (N-methyl- D-aspartic acid) 수용체에대한길항제로심혈관계및호흡억제작용이없고강력한진통작용이있다는점이장점이다 [18,19]. 하지만억제성아미노산수용체인 glycine 수용체반응을억제하여흥분작용도가지게되어수술후회복시악몽, 섬망등의부작용을야기한다고알려져있다 [20]. 이런점에도불구하고수술실입구에서심한흥분과불안상태를보이는소아를수술실로이송하기위한목적으로 ketamine을많이사용한다. 저용량의 ketamine 1.0 mg/kg의사용은진정과진통작용을가지고있어서오히려각성섬망의빈도를줄일수있다는연구결과들도있다 [21]. 그러나본연구에서는마취유도용량인 2.0 mg/kg의 ketamine을사용하였고, 부안검교정수술은수술시간이대략 1시간이내이므로각성섬망에미치는영향이수술후회복실에서까지도남아있었을가능성을배제할수없다. 마취유지에사용된 sevoflurane 역시각성섬망을일으킨다고알려져있다. Sevoflurane은소아마취에서널리이용되는할로겐화흡입마취제이다. 그이유로첫째는 sevoflurane 의심혈관계안정성때문이고 [22] 둘째는혈액과조직에용해도가낮아마취의유도와각성이빠르고 [23,24] 셋째는기도자극이적어부드러운마취유도가가능하며또한간독성이적기때문이다 [25]. 그러나최근연구에의하면 sevoflurane의마취유도와각성시 halothane 혹은 propofol보다흥분과섬망을더잘일으킨다고알려져있고각성시섬망발생의빈도를 67% 까지증가시킨다고보고되었다. Lerman 등은 sevoflurane 마취후각성섬망이증가되는이유는빠른회복후에나타나는술후통증과 ether 결합을가진흡입마취제에서나타날수있는중추신경계효과때문이라는가설을제시하였다 [26]. 또한서혜부탈장을교정받는환아를미추차단한후 sevoflurane으로마취한경우에 halothane에비해각성흥분의빈도가더높다는보고도있다 [27]. Wells 등은 sevoflurane 마취후나타나는섬망은주변환경을잘못인지하여발생한다고하였다 [28]. 이런결과로볼때 sevoflurane 마취와관련해서는통증이외에각성흥분을유발하는다른요소도분명히있는것으로보인다. 이러한점들을종합할때본연구에서대조군과실험군의유의한차이를얻지못한우선적인이유는술후통증이비교적경미한수술을대상으로하였기때문에통증이외에각성흥분을유발하는다른인자들의영향이상대적으로더컸었기때문이라고생각된다. 소아의각성섬망에대한연구들은편도절제술이나서혜부탈장수술과같이술후통증조절이중요한수술을대상으로대부분의연구가이루어져온반면에안과수술과같이술후통증이적은수술을받는소아환자에서도각성섬망이발생한다는점에서이러한수술에서도비록통증의정도가상대적으로약 할지라도통증을줄이는것이각성섬망에미치는영향이어느정도인지를알아보는것도필요하다고생각된다. 본연구의결과로보면부안검교정술을받는소아에서술전에정주한 acetaminophen의선제진통효과는미미하다고판단되며, 이러한수술을받는환아들에서각성섬망을줄이기위해서는통증제어에적절한시점에진통제를투여하며조용한환경에서소아를회복시키고소아가완전히회복될때까지자극을피하며 ketamine, scopolamine, droperidol 등의술후흥분과관련이있는약물의사용을피하는것이바람직하다 [29]. 본연구에서부족했다고생각되는점은회복실에서 FLACC (face, legs, agitation, crying, consolability), CHEOPS (Childrens Hospital of Eastern Ontario Pain Scale), NIPS (Neonatal Infant Pain Scale), Faces Pain Scale, Poker Chip Tool, Visual Analogue Scale 등을이용하여환아의통증정도를측정했다면통증이술후섬망에미치는영향에대해더욱직접적인연관성을논할수있었을것이라는점이다. 하지만이러한통증정도의평가도대개의사, 간호사, 또는보호자에의해평가됨으로써그효과를예측하기가힘들고주관적인결과라는한계점이있다. 또한회복실에서각성섬망의측정을회복실도착 10분간의관찰후그결과를측정했는데, 각성시흥분은회복기의초기 10분동안가장빈번히발생한다고하지만, 회복실에도착후많은소아들이잠에서깨면서각성시흥분이늦게나타날수도있다는점을바탕으로회복실도착후 10분이후에도지속적인관찰을하여결과에반영하는것이보완해야할점이다. 결론적으로부안검교정술을받는소아에서술전에정주한 acetaminophen은술후각성섬망의발생을감소시키지않았으며, 위에서언급한본연구의문제점들을보완한후속연구가필요하다고생각한다. 참고문헌 1. Cohen IT, Motoyama EK. Intraoperative and postoperative management. In: Smith's anesthesia for infants and children. 6th ed. Edited by Motoyama EK, Davis PJ: St. Louis, Mosby. 1996, pp Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, et al. Opioid complications and side effects. Pain Physician 2008; 11(2 Suppl): S Kim YH, Park MH, Son SC, Choi SJ. The effect of acetaminophen rectally administrated before operation on postoperative pain and behavior after tonsillectomy in small children. Korean J Anesthesiol 1997; 32: Wallenstein MC. Differential effects of prostaglandin synthetase inhibitors on EEG in rats. Eur J Pharmacol 1990; 111: Olstad O, Skjelbred P. The effects of ibuprofen vs paracetamol on

5 임연희외 4 인 : 술전 acetaminophen 투여와소아각성섬망 259 swelling, pain, and other events after surgery. Int J Clin Pharmacol Ther Toxicol 1986; 24; Skoglund L, Skjelbred P. Comparison of a traditional paracetamol medication and a new paracetamol/paracetamol methionine ester combination. Eur J Clin Pharmacol 1984; 26: Murat I, Baujard C, Foussat C, Guyot E, Petel H, Rod B, et al. Tolerance and analgesic efficacy of an new iv paracetamol solution in children inguinal hernia repair. Paediatr Anaesth 2005; 15: Moller PL, Juhl GI, Payen-Chanpenosis C, Skoglund LA. Intravenous acetaminophen(paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery. Anesth Analg 2005; 101: Aono J, Ueda W, Mamiya K, Takimoto E, Manabe M. Greater incidence of delirium during recovery from sevoflurane anesthesia in preschool boys. Anesthesiology 1997; 87: Veyckemans F. Excitation and delirium during sevoflurane anesthesia in pediatric patients. Minerva Anestesiol 2002; 68: Finkel JC, Cohen IT, Hannallah RS, Patel KM, Kim MS, Hummer KA, et al. The effect of intranasal fentanyl on the emergence characteristics after sevoflurane aneshtesia in children undergoing surgery for bilateral myringotomy tube placement. Anesth Analg 2001; 92: Viitanen H, Annila P, Viitanen M, Tarkkila P. Premedication with midazolam delays recovery after ambulatory sevoflurane anesthesia in children. Anesth Analg 1999; 89: Cravero JP, Beach M, Thyr B, Whalen K. The effect of small dose fentanyl on the emergence characteristics of pediatric patients after sevoflurane anesthesia without surgery. Anesth Analg 2003; 97: Savarese JJ, Caldwell JE, Lien CA, Miller RD. Pharmacology of muscle relaxants and their antagonist. In. Anesthesia. 4th ed. Edited by Miller RD, Cucchiara RF, Miller ED, Reves JG, Roizen MF, Savarese JJ: New York, Churchil Livingstone Publishers. 1994, pp Buckley MM, Brogden RN. Ketorolac. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. Drugs 1990; 39: Lee IH, Han JI, Kim DY, Lee GY. The effect of ketorolac and propacetamol on pain control after tonsilectomy in pediatric patients. Korean J Anesthesiol 2008; 55; Lee JM, Kim HG, Lee JH, Lee SG. The effect of alfentanil on the emergence agitation after sevoflurane anesthesia in children undergoing inguinal herniorrhaphy. Korean J Anesthesiol 2005; 49; Lee IO. Pre-emptive Analgesia: the effect of low-dose ketamine on the postoperative pain after circumcision with unilateral hydrocelectomy in children. Korean J Anesthesiol 1998; 35: Chon S, Yoon DM, Kim J, Ahn EK, Kang SH, Keum CM. Control of postinguinal herniorrhaphy pain in children. Korean J Anesthesiol 2004; 47: Lee BR, Oh SW, Jung YH. The comparison of characteristics in emergence between inhalational anesthesia using isoflurane and total intravenous anesthesia using propofol and ketamine. Korean J Anesthesiol 2002; 43: White PF, Way WL, Trevor AJ. Ketamine-its pharmacology and therapeutic uses. Anesthesiology 1982; 56: Holtzman RS, van der Velde ME, Kaus SJ, Body SC, Colan SD, Sullivan LJ, et al. Sevoflurane depresses myocardial contractility less than halothane during induction of anesthesia in children. Anesthesiology 1996; 85: Sarner JB, Levine M, Davis PJ, Lerman J, Cook DR, Motoyama EK. Clinical characteristics of sevoflurane in children. A comparison with halothane. Anesthesiology 1995; 82: Piat V, Dubois MC, Johanet S, Murat I. Induction and recovery characteristics and hemodynamic responses to sevoflurane and halothane in children. Anesth Analg 1994; 79: Johannesson GP, Floren M, Lindahl SG. Sevoflurane for ENT-surgery in children. A comparison with halothane. Acta Anaesthesiol Scand 1995; 39: Lerman J, Davis PJ, Welborn LG, Orr RJ, Rabb M, Carpenter R, et al. Induction, recovery, and safety characteristics of sevoflurane in children undergoing ambulatory surgery. A comparison with halothane. Anesthesiology 1996; 84: Weldon BC, Bell M, Craddock T. The effect of caudal analgesia on emergence agitation in children after sevoflurane versus halothane anethesia without surgery. Anesth Anlag 2003; 97: Wells LT, Rasch DK. Emergence "delirium" after sevoflurane anesthesia: a paranoid delusion? Anesth Analg 1999; 88: Veyckemans F. Excitation phenomena during sevoflurane anesthesia in children. Curr Opin Anaesthesiol 2001; 14:

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