Anesth Pain Med 28; 3: 25 254 임상연구 소아오목가슴수술후정맥통증자가조절시 Ondansetron 의투여방법이수술후오심및구토에미치는효과 고려대학교의과대학마취통증의학교실 신연식ㆍ김재환ㆍ백성문ㆍ이윤숙ㆍ김운영ㆍ장문석ㆍ박영철 The effect of methods of ondansetron administration on nausea and vomiting during intravenous patient-controlled analgesia in pediatric patients undergoing pectus excavatum repair Youn-sik Shin, M.D., Jae Hwan Kim, M.D., Sung-Moon Baek, M.D., Yoon-Sook Lee, M.D., Woon Young Kim, M.D., Moon-Seok Chang, M.D., and Young Cheol Park, M.D. Department of Anesthesiology and Pain Medicine, Korea University College of Medicine, Seoul, Korea Background: Postoperative nausea and vomiting remain troublesome problems, especially in pediatric patients receiving the opioid analgesics. This study was designed to evaluate the difference between bolus injection and continuous infusion of ondansetron for the prevention of postoperative nausea and vomiting in pediatric patients with intravenous patient-controlled analgesia (IV-PCA). Methods: Sixty patients undergoing pectus excavatum repair were randomly assigned into three groups, no antiemetic (, n = 2), intraoperative ondansetron.1 mg/kg IV bolus (, n = 2), ondansetron.1 mg/kg mixed with IV-PCA (, n = 2). The incidence of nausea, vomiting, the need for rescue antiemetics, side effects and pain score were recorded for 48 hr postoperatively. Results: The incidence of nausea in (2%) and Group 3 (25%) was significantly lower than (6%). There was no significant difference in the incidence of vomiting among the groups (:6%, :2%, :2%). The need for rescue antiemetics was significantly lower in and 3 than. Conclusions: In pediatric patients undergoing pectus excavatum repair, bolus injection and continuous infusion of ondansetron were effective in preventing postoperative nausea during IV-PCA. And 논문접수일 :28 년 9 월 2 일책임저자 : 김재환, 경기도안산시단원구고잔동 516 번지고려대학교안산병원마취통증의학과우편번호 : 425-77 Tel: 31-412-5295, Fax: 31-412-5294 E-mail: anejhkim@korea.ac.kr 석사학위논문임. the need for rescue antiemetics was significantly decreased. (Anesth Pain Med 28; 3: 25 254) Key Words: intravenous patient-controlled analgesia, nausea and vomiting, ondansetron, pectus excavatum. 서 오목가슴수술은금속막대를환자의흉부기형에맞게활처럼구부린후, 가슴양옆구리에피부를절개하고함몰된흉골부위와심장사이로금속막대를통과시킨뒤휘어진바깥면이함몰된늑골과흉골을밀어올리게하여정상적인가슴모양을만드는수술이다. 1) 수술후흉곽이팽창됨으로인해수술후심한통증을유발하므로통증을경감시키는방법으로진통제를경막외강을통해주입하거나 2) 정맥내지속주입하는방법이 3) 사용된다. 하지만마약성진통제를이용한정맥자가통증조절법은오심과구토로인해환자의만족도가감소하거나불쾌감과고통을호소하게된다. 4) Ondansetron은 5-HT 3 수용체를선택적으로길항하는 serotonin 길항제로서수술후오심과구토에효과가있다고알려져있다. 5) Ondansetron의일회투여가소아수술후오심과구토를줄인다는연구는 6) 많지만, ondansetron의수술중일회투여와지속투여의효과에대한직접적인비교는없다. 본연구에서는소아오목가슴수술에서 ondansetron을일회투여하는경우와지속적으로투여하는경우를비교하여 ondansetron의투여방법이정맥통증자가조절시수술후오심과구토에미치는영향에대하여알아보았다. 론 대상및방법 오목가슴수술이예정된 3 14세의소아환자중미국마취과학회신체등급분류 1, 2에속하는 6명의환자를대상으로병원윤리위원회의승인을받은후수술전보호자에게통증자가조절법과본연구에대한동의를구하였다. 특이질환을가지고있는환자나오심과구토의잦은기왕 25
신연식외 6 인 :Ondansetron 투여방법이오심및구토에미치는효과 251 력이있는환자의경우는대상에서제외하였다. 마취유도 3분전에마취전처치로 atropine.1 mg/kg을근주하였으며수술실에도착한후환자감시장치 (Solar 8M, GE Medical, USA) 로심전도, 혈압, 맥박산소포화도를측정하였다. 마취의유도를위해서 thiopental sodium 5 mg/kg와 rocuronium.6 mg/kg를정주하고기관내삽관을시행하였다. 마취유지는아산화질소 (2 L/min) 와산소 (2 L/min) 를각각 5% 로흡입시키고 sevoflurane을호기말농도 2. vol% 로유지하였다. 통증조절은수술종료직전, 피부봉합이거의완료되었을때부하용량으로 fentanyl 1.μg/kg를정주하고, 통증자가조절장치 (AutoMed 32, Acemedical, Korea) 를이용하여 fentanyl 지속주입속도가.5μg/kg/hr이되도록생리식염수에혼합하여총 6 ml용액으로만들어시간당 1 ml의속도로주입하였고, 환자가통증을느낄때환자나보호자가요구버튼을누르면.5 ml가추가로주입되도록하였으며횟수는시간당 2회로제한하였다. 환자들을무작위로세군으로나누어 1군은생리식염수.5 ml/kg를수술종료직전정주하였고, 2군은 ondansetron.1 mg/kg를수술종료직전정주하였다. 3군은생리식염수.5 ml/kg를수술종료직전정주하고, ondansetron.1 mg/kg를통증자가조절장치에혼합하여지속적으로주입되도록하였다. 환자는수술후 6, 12, 24, 48시간에통증정도, 주입된 PCA의용량, 오심과구토, 기타부작용발생여부를측정하였다. 통증정도는 Faces Scale (FS) 과 7) the Face Legs Activity Cry and Consolability (FLACC) Behavioral Pain Assessment Scale를 8) 이용하여측정하였고, 오심은환자가호소하는정도에따라 4 point scale (:none, 1:mild, 2: moderate, 3:severe) 로 9) 나누어기록하였고, 위내용물을입밖으로토한경우구토로기록하였다. 환자가오심과구토를참기어려워하여항구토제를요구하는경우 ondansetron.5 mg/kg를정주하고그시간을기록하였다. 통계분석은 SPSS (version 13.) 을이용하였으며환자의특성, 통증정도, ondansetron 투여횟수는 one-way ANOVA, 사후검정은 Scheffe test를사용하였고, 오심및구토와기타부작용의발생율은 Chi-square test를이용하였으며, P <.5인경우통계적으로유의하다고판정하였다. Table 1. Demographic Data Age (yr) Sex (M/F) Weight (kg) Operative time (min) Total infused fentanyl dose, (mg/kg) 6.7 ± 3.5 16/4 22.5 ± 9.8 118.9 ± 22.8 27.1 ± 1.5 6.4 ± 3.6 16/4 22.3 ± 9.6 17.3 ± 29.9 26.2 ± 1. 6.3 ± 3. 15/5 22.2 ± 1.8 116.3 ± 21. 26.7 ± 1.6 Value are mean ± SD. There were no significant differences among the groups. : control, : bolus injection of ondansetron, : continuous infusion of ondansetron. Table 2. Incidences of Postoperative Nausea, Vomiting and Rescue Antiemetics during Each Period Nausea Vomiting PONV Rescue antiemetics 6 (3%) 13 (65%) 5 (25%) * * 6 (3%)* * * * 5 (25%)* 5 (25%) 5 (25%)* * * Values are numbers of patient (%). : control, : bolus injection of ondansetron, : continuous infusion of ondansetron. *: P <.5 compared with. 결과대상환자의연령, 체중, 수술시간, 48시간동안투여된 fentanyl의양은각군간유의한차이는없었다 (Table 1). 수술후 48시간동안의오심의발생은 1군 12명 (6%), 2 군 4명 (2%), 3군 5명 (25%) 으로 1군에비해 2군과 3군에서오심의빈도가유의하게낮았다. 구토를한환자는각군간유의한차이는없었다. 중등도이상의오심을호소하거나구토를하여항구토제를요구한환자는 1군 12명 (6%), 2군 4명 (2%), 3군 4명 (2%) 으로 1군에비해 2군과 3군에서항구토제의투여가유의하게적었다. 시간에따른빈도에서는수술후 12 24시간에서 1군에비해 2군과 3군에서수술후오심의빈도 (1군 55%, 2군 1%, 3군 2%) 와항구토제의투여빈도 (1군 55%, 2군 1%, 3군 15%) 가유의하게낮았다 (Table 2). 수술후 6, 12, 24, 48시간의통증정도는각군간유의한차이는없었다 (Table 3). 수술후진정, 어지러움, 두통, 변비등의부작용은세군
252 Anesth Pain Med Vol. 3, No. 4, 28 Table 3. Postoperative Pain Score using a Faces Scale (FS) and the Face Legs Activity Cry and Consolability (FLACC) FS 6 hr 12 hr 24 hr 48 hr FLACC 6 hr 12 hr 24 hr 48 hr 2.6 ±.9 2.4 ±.7 1.9 ±.8 1.5 ±.5 3.2 ± 1.3 2.9 ± 1.3 2.5 ± 1.6 1.8 ±.9 3.2 ±.8 2.6 ±.9 2.4 ±.8 1.9 ±.6 4.3 ± 1.6 3.6 ± 1.6 3. ± 1.3 2.2 ± 1.1 3. ±.6 2.2 ±.4 2. ±.6 1.5 ±.6 4.3 ± 1.9 3.1 ± 1.8 2.6 ± 1.7 2. ± 1.1 Value are mean ± SD. There were no significant differences among the groups. : control, : bolus injection of ondansetron, : continuous infusion of ondansetron. 간유의한차이는없었으나세군모두약 5% 의빈도로변비를호소하였다 (Table 4). 고 수술후오심과구토 (Postoperative Nausea and Vomiting, PONV) 를발생시키는원인은환자의요인과수술및마취의요인으로분류되며, 환자의성별 ( 여자 ), 나이 ( 젊은나이 ), 체중 ( 과체중 ), 과거력 ( 이전의 PONV나멀미 ), 흡연 ( 비흡연자 ), 전신상태 ( 건강인, 낮은미국마취과학회신체등급분류 ) 등이환자와관련된위험인자로알려져있고, 수술의종류및시간, 수술중, 후의아편유사제의사용, 마취제의종류 ( 흡입마취제, N 2O, Etomidate) 등이수술과마취에관련된위험인자로알려져있다. 1) 소아는성인에비해오심과구토의빈도가높고여아인경우, 편도절제술, 사시수술, 탈장수술, 중이수술, 복강경수술인경우, 수술시간이긴경우, 수술중이나수술후아편양제제를사용한경우등에서오심과구토의빈도가높다고알려져있다. 11) 본연구는 PONV의발생이높을것으로예측되는소아환자에서 1시간이상의수술시간이필요하고아편양제제를이용한정맥통증자가조절장치 (intravenous patient-controlled analgesia, IV-PCA) 를사용하는경우를대상으로하였다. 아편양제제를이용한통증자가조절장치를사용한환자에서 PONV의빈도는 Benzon 등은 12) 3 5% 로보고하였다. 소아에서 morphine을이용한 IV-PCA를사용한경우 PONV 의빈도는 54 83% 정도로다양하였다. 13,14) Ahn 등은 15) 오목가슴수술을받는소아환자를대상으로 fentanyl을이용한 IV-PCA 연구에서 PONV의빈도가 5 55% 라고보고하였고, 본연구에서 ondansetron을투여하지않은대조군의 찰 Table 4. Incidence of Side Effects Sedation (%) Dizziness (%) Headache (%) Constipation (%) 1 (5%) Values are numbers of patient (%). There were no significant differences among the groups. : control, : bolus injection of ondansetron, : continuous infusion of ondansetron. PONV 의빈도는 6% 로비슷하였다. 아편양제제를사용한 IV-PCA 사용시 PONV를완화시키기위하여여러가지항히스타민제, 항콜린제, 도파민수용체길항제가사용되어왔으나진정작용이나추체외로증상등의부작용이있어최근에는 5-HT 3 수용체의선택적인길항제인 ondansetron이부작용없이오심, 구토를예방하는데많이사용되고있다. 16) IV-PCA 사용시 ondansetron의일회투여의효과에대한연구에서 Kim 등은 4) 어느시기든지 ondansetron을일회투여하면수술후오심과구토의억제효과가나타난다고하였고, ondansetron을지속투여한연구에서 Hwang 등은 17) 척추수술을받는성인환자를대상으로 IV-PCA에 ondansetron 8 mg을섞어서지속투여한군이 ondansetron을지속투여하지않은군에비해오심과구토가감소한다고보고하였다. 소아환자를대상으로한연구를살펴보면 Lawhorn 등 은 18) 수술후오심과구토의위험이높은편도절제술이나사시수술을시행받는소아환자에서 ondansetron의일회투여가 ondansetron을투여하지않은경우에비해 PONV의빈도를줄인다고보고하였다. Ondansetron의지속투여에대한연구에서 Munro 등은 19) 충수절제술을시행한소아환자를대상으로수술중 ondansetron을일회투여하고 IV-PCA와함께지속정주한경우 ondansetron을투여하지않은경우와오심과구토의빈도의차이는없다고하였다. 그러나소아나성인모두 ondansetron의일회투여에대한효과와지속투여에대한효과를동일연구에서직접비교하고조사한경우는없었다. 본연구에서는 ondansetron을지속투여한경우와일회투여한경우를직접비교하였다. Ondansetron을투여하지않은경우에비해 ondansetron을일회투여한경우와지속투여한경우모두수술후오심의빈도는유의하게감소하였다. 하지만 ondansetron을일회투여한경우와지속투여한경우사이에오심의빈도는차이가없었다. 항구토제의사용역시 ondansetron을일회투여하거나지속투여하는경우에서 ondansetron을투여하지않은경우에비해수술후 ondansetron
신연식외 6 인 :Ondansetron 투여방법이오심및구토에미치는효과 253 의투여가줄었지만, 일회투여한경우와지속투여한경우사이에유의한차이는없었다. 이는 ondansetron의제거반감기가 3 4시간으로비교적짧지만항구토작용은 24시간가량지속되므로 2) 일회투여하였을경우와지속투여하였을경우의차이가없다고생각된다. McKenzie 등은 21) 산부인과수술환자대상의연구에서 ondansetron의작용시간은 24시간이상지속된다고하였고, Goodarzi 등은 22) 정형외과수술후경막외 fentanyl로통증조절을하는소아환자에서 ondansetron 일회투여가 48시간동안의오심의빈도를낮춘다고보고하였다. 본연구에서시간에따른 PONV의빈도를보면 ondansetron 을투여하지않은경우수술후 12 24시간에서오심의발생이가장많았다. Apfel 등은 23) 흡입마취제의사용이수술후 2시간이내에발생하는초기 PONV의주요원인이고, 소아, 수술후아편양제제의사용이수술후 2시간에서 24시간사이에서발생하는후기 PONV의주요원인으로보고하였다. 본연구에서 ondansetron을투여하지않은경우수술후 12 24시간에서오심의발생이가장많았던것은흡입마취제의영향보다는대상이소아환자이고수술후아편양제제가지속정주되었기때문이라고생각된다. 수술후 24 48시간의오심의발생은세군간에차이가없었다. 이는수술후 12 24시간에투여된추가항구토제의영향에의해 24시간이후의오심의빈도가줄어들었거나오심에대한내성이생겼기때문이라고생각된다. 아편양제제의부작용중오심과구토에대한내성은다른부작용에비해빨리수시간에서수일내에생긴다고알려져있다. 본연구에서수술후구토의발생은세군간차이가없었다. Tramer 등은 24) ondansetron에대한연구에서항구토작용이항오심작용보다뚜렷하다고하였다. 하지만 Tramer 등은구토에위내용물이입밖으로나오는것과구역질 (retching) 까지포함시켜서비교한데비해본연구에서는구토의정의를위내용물이입밖으로나오는것에만한정했기때문에결과가다르게나온것으로사료된다. 본연구에서모든오심과관련된증상을합하여비교하였을때 ondansetron 을투여하지않은경우에비해 ondansetron을일회투여한경우와지속정주시킨경우모두 PONV 빈도는유의하게감소하였다. 오목가슴수술은수술후흉곽이팽창됨으로인해수술후심한통증을유발하므로통증을경감시키는방법으로진통제를경막외강을통해주입하거나정맥내지속주입하는방법이사용된다. 하지만소아의경우경막외강을통한주입방법은시술의어려움이있고중대한합병증을일으킬수도있다. Butkovic 등은 32) 오목가슴수술을시행받는소아환자에서 fentanyl을이용한 IV-PCA가경막외차단과마찬가지로효과적인진통효과를보인다고하였고, 경막외진통의합병증이염려되는경우는 IV-PCA를추천한다고하였다. 소아환자에있어서통증의평가방법에는생리학적인기술 (physiology technique), 행동관찰 (behavioral observation), 환자호소 (patient report) 등이있다. 25) Faces scale은소아에서가장대중적으로사용되는통증을호소 (children's self-reports of pain) 하는방법이고, 26) FLACC 행동평가방법은병원내에서수술후통증을평가하는가장좋은방법이다. 27) Ondansetron은항구토작용이외에도국소마취제의특성을갖고있다는보고가있으며 propofol 정주전에투여하여통증을완화시킬수있다고하였다. 28) 하지만 Derbent 등의 29) 연구에서는 ondansetron이척추후굴절제술을시행받은환자의진통제요구량을감소시키지못하였고, 본연구에서도 ondansetron의투여에따른세군간의통증지수와 48시간동안 fentanyl의총투여량의차이는나타나지않았다. Ondansetron의부작용으로는두통, 진정, 어지러움, 변비, 설사, 근육통등이있으며 3) 본연구에서는각군간부작용의차이는보이지않았다. 변비의경우 5% 이상의환자에서나타났고이는 IV-PCA에포함된아편양제제의부작용에의한것으로생각된다. 아편양제제는위장관의아편수용체를직접활성화시키고위액감소, 장체류시간연장, 장벽에서수분흡수증가가일어나변비가유발된다. Flogegard 등 은 31) 소아암환자에서통증완화를위해 morphine을지속정주하는경우변비가 24% 발생하였다고보고하였으며, Ahn 등은 17) 오목가슴수술을받는소아환자에서 fentanyl을이용한 IV-PCA를사용하였을때변비의발생율이 7% 라고보고하였다. 변비가있는환자에서수술부위의통증보다변비로인한복부통증을호소하는경우가많았으며, 관장을한후에는복부통증이줄어들었다. 아편양제제를이용한 IV-PCA 사용시변비로인한복부통증을줄이기위하여배변완화제의사용이고려되어야할것으로사료된다. 결론적으로, 오목가슴수술을받는소아환자에서 fentanyl 을이용한정맥통증자가조절시, ondansetron.1 mg/kg의일회투여와지속투여모두 ondansetron을투여하지않은대조군에비하여수술후오심의빈도와항구토제투여빈도의유의한감소가나타났다. 따라서두방법모두소아환자에서수술후오심과구토를효과적으로조절할수있는유용한방법으로생각된다. 참고문헌 1. Nuss D, Kelly RE, Croitoru DP, Kartz ME: A 1-year review of minimally invasive technique for the correction of pectus excavatum. J Pediatr Surg 1988; 33: 545-52. 2. McBride WJ, Dicker R, Abajian C, Vane DW: Continuous thoracic epidural infusions for postoperative analgesia after pectus deformity repair. J Pediatr Surg 1996; 31: 15-8. 3. Thomas ARL: Pain management in pediatric patients. Br J Anaesth 199; 64: 85-14.
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