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1 E-III. 진정내시경 : 기초에서응용까지 Room E 연세대학교원주의과대학내과학교실 Sedative Endoscopy in Special Circumstances Hong Jun Park Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea 서론 진정내시경은진정약물을사용하여환자가시술을받는동안불안함을감소시켜주고일정시간동안의기억상실을유발하기위하여사용된다. 적절한진정이란환자가주관적으로편안하게느끼는상태를유발하는동시에기도반사가유지되어안정적으로자발호흡을유지하며의료진의요구에협조가가능한정도의의식상태를지속하는것이다. 1 일반적으로진정내시경은적절한용법과감시로대부분큰문제없이시행될수있으나, 고령, 산모, 수유부, 소아, 만성간질환및호흡기질환환자등에있어서는진정으로인한합병증의가능성이높기때문에안전한진정내시경을위한준비가필요하다. 본고에서는이러한상황에서고려해야할사항과적절한수면에대하여알아보도록하겠다. 본론 1. 고령환자의진정내시경 최근평균연령이높아짐에따라고령인구가증가하고있으며고령인구에대한진정내시경또한증가하고있다. 내시경을이용한선별검사나치료내시경등을언제까지시행해야하는지나이를기준으로결정된사항은없으나일반적으로 세이상의초고령환자에서도내시경검사는대부분금기사항은아니다. 2 고령환자에서도진정내시경은편안한방법이지만, 젊은환자와비교하여고령환자가가지는몇가지특징을이해하는것이더안전한검사를위하여필요하다. 3 한연구에서는젊은환자와비교하였을때같은중등도진정 (moderate sedation) 에서고령환자에게더쉽게저산소증이발생한다고보고를하고있다. 4 이는고령환자특히, 심혈관계질환또는호흡기질환을가지고있는고령환자의경우는대부분환기 관류불균형에따른만성적인고탄산혈증이가지고있어서저산소증이나고탄산혈증에대한중추신경계의반응이감소되어있기때문이다. 5 따라서쉽게저산소증이나타날수있어서산소포화도에대한면밀한감시가필요하다. 또한, 고농도의산소를빨리투여하게되면오히려호흡이억제될수있어서산소공급시주의해야한다. 고령의환자에게는반사적으로성문이닫히는감각역치가증가함에따라성문반사가감소해있으며진정제투여시성문반사가더욱감소할수있어서상부위장관내시경의합병증으로흡인성폐렴이발생할가능성이높다. 6 고령에서약물의흡수, 대사, 배설이저하되어약물농도가증가하고이에따른회복시간지연이나타날수있다. 연령이높아질수록근육량이감소하고신체질량 (body mass) 에대한지방비율이증가하여지용성인 benzodiazepine 의경우체내분포면적이증가하게된다. 지용성약물의체내분포면적증가는대사과정을지연시켜약제의임상적효과를현저히증가시킬수있다. 일반적으로고령에서진정내시경시합병증이더잘발생하는이유는고령자체의영향이라기보다는고령과관련된만성질환의이환과약제의용량및빠른투여와연관되어있다. 7 따라서진정약물은성인용량의절반부터서서히투여하는것이안전한방법이다. 8,9 저산소증에대한적극적인감시와필요시저농도의산소부터서서히투입, 흡인성폐렴예방을위해내시경전 후적극적인구강내흡인이합병증을예방하기 제 50 회대한소화기내시경학회세미나 285

2 Table 1. 미국소화기내시경학회에서권고하는임산부에서내시경가이드라인 15 General principles guiding endoscopy in pregnancy Every endoscopic procedure requires a preoperative consultation with an obstetrician, regardless of fetal gestational age. Always have a strong indication, particularly in high risk pregnancies. Defer endoscopy to second trimester whenever possible. Use lowest effective dose of sedative medications. Use category B drugs whenever possible. Minimize procedure time. Position patient in left pelvic tilt or left lateral position to avoid vena cava or aortic compression. The decision to monitor fetal heart rate should be individualized and will depend on gestational age of the fetus and available resources. Before 24 weeks of fetal gestation, it is sufficient to confirm the presence of the fetal heart rate by Doppler before sedation is begun and after the endoscopic procedure. After 24 weeks of fetal gestation, simultaneous electronic fetal heart and uterine contraction monitoring should be performed before and after the procedure. Ideally, procedures should be done at an institution with neonatal and pediatric services. If possible, the fetal heart rate and uterine contractions should be monitored before, during, and after the procedure by a qualified individual, with obstetric support readily available in case of fetal distress or a pregnancy related complication. Endoscopy is contraindicated in placental abruption, imminent delivery, ruptured membranes, or uncontrolled eclampsia. 위한방법이될수있다. 약제는젊은환자들과마찬가지로 midazolam 사용에는큰문제가없다. 또한, Propofol 은좁은안전역을가지고있지만최근보고에의하면고령환자에게서도안전하다고알려져있다 진정보조또는통증조절을위해서 meperidine 을사용할때는발현효과가더빠르고반감기가짧은 fentanyl을사용하는것이바람직하다 임신및수유중진정내시경 Table 2. 내시경과관련된약제들의 FAD category 16 Drug FDA category in pregnancy* Summary of literature regarding drug safety Narcotics Meperidine B, but D at term Human data suggest some risk if used for prolonged periods or in high doses at full term 3 Fentanyl C Human data suggest some risk when used in the third trimester Propofol B Limited human data; animal data suggest General anesthetics Ketamine B Limited human data; animal data suggest 17 Sedatives Diazepam D Human data suggest possible risk when used in first and third trimesters 17 Midazolam D Limited human data; animal data suggest Reversal agents Naloxone B Probably safe on the basis of several studies in humans Flumazenil C Limited human data; animal data suggest *If drug safety during pregnancy is not rated by the FDA, the semiauthoritative drug rating by Briggs et al. 3 is substituted. 임신중시행되는내시경의안정성과효과에대하여는잘연구된바가없으며대부분작은규모나후향성연구및약제안전성결과에따른권고사항이대부분이다. 미국소화기학회에서는임산부에서내시경은꼭필요한적응증하에서시행하도록권장하고있다 (Table 1). 14,15 진정내시경과관련하여, 태아는산모의저산소증및저혈압에민감하기때문에과도한진정에대하여주의하여야한다. 대부분의시술은가벼운진정상태 (anxiolysis) 또는중등도의진정상태에서시행되어야하며만약깊은진정상태가요구될경우에는마취과의사에의해진정제가투여되어야한다. 임신과관련하여나타날수있는생리적변화중구 인두조직의부종, 성문개구부가줄어드는심 폐기관의변화를미리인지하고있어야하며, 진정내시경시주의깊은감시가요구된다. 15 또한약제에의한기형유발이나조산등에도주의가필요하며필요시산부인과의사의조언을구해야한다. 임신중약제에관련하여 FDA에서는 5개의분류 (catergory A, B, C, D, X) 를이용하여구분하고있다. 내시경과관련하여 category A인약제는없다. 따라서, category B 또는 C의약제까지사용이가능하다. FDA category 중 meperidine, naloxone, propofol, 국소마취제인 lidocaine은 category B로 fentanyl, flumazenil, simethicone 등은 category C, 그리고 benzodiazepines 계열인 midazolam이 category D로분류된다 (Table 2). 16 Propofol 은안전역이좁아서잘숙련된마취과의사와상의하여사용되어야한다. 그렇지만임신첫 3개월이내에 propofol의안정성에대해서는연구가불충분하다. 17,18 Bensodiazepine 계열약제중 diazepam 은임신말기구순열및신경행동장애와관련될수있으므로사용하면안된다. 19, Korean Society of Gastrointestinal Endoscopy

3 Table 3. 수유부에대한진정약물사용의미국소화기학회권고사항 15 We suggest that breastfeeding may be continued after maternal fentanyl administration. We suggest that infants not be breastfed for at least 4 hours after maternal midazolam administration We suggest that breastfeeding may be continued after maternal propofol administration as soon as the mother has recovered sufficiently from general anesthesia to nurse. Midazolam은선천성기형과관련이없어서임신 1분기를제외한나머지기간에 meperidine 으로진정이부족한경우사용해볼수있다. 21 국소마취제로사용하는 lidocaine 은 category B로사용이가능하지만, 한연구에서임신 1분기에 lidocaine 에접촉한경우일부에서기형발생을보고하여가능하면 lidocaine 을이용한목마취후삼키지말고뱉는것이좋다. 22 수유부에대한진정내시경시합병증의위험도는일반정상성인의위험도와비슷하다. 23 그렇지만수유시약제가모유를통해영아에게전달될수있다. Midazolam 투여후최소 4시간안에수유하지않도록권고하고있으며, meperidine 는투여 24시간후에도모유에서검출되므로가능한사용을피하고, fentanyl 은모유를통해전달될수있는양이매우적어수유를중단할필요가없다고권고하고있다. 15 Propofol 은투여후 4 5시간째최고농도로모유에서검출되나언제까지수유를중단해야하는지에대해서는아직까지알려지지않았다. 24 미국소화기학회에서는수유부가 propofol 투여후충분히회복된이후가능하리라제안하고있다 (Table 3). 15 환자에게는수유가금지된시간까지모유를짜서버릴것이권고된다. 3. 소아에서의진정내시경 소아에서도비진정내시경이가능하지만환아에게불안감을없애고, 안심시켜서협조를유도하기위해대부분진정내시경이시행된다. 미국소아과학회에서는소아진정내시경시행시모든진정상태에서산소투여및지속적인맥박, 산소포화도측정이필수적이며깊은진정상태인경우, 소아의활력징후모니터링만을시행하는인원이필요하며, 또한소아심폐소생술에대해제대로교육받은인력이꼭필요하다고권고하고있다. 25,26 소아진정내시경에사용되는약제는 propofol 의빠른유도시간과짧은지속시간으로안전하면서효과적이라고알려져있다. 27,28 811명의소아내시경시술에서 propofol 을이용한진정시에심각한저산소증의빈도는 0.7% 였으며, 99.6% 에서성공적으로검사를수행하였다고보고되었다. 29 Propofol 에 midazolam 이나 fentanyl 을추가함으로써부작용을높이지않으면서효과를높이는방법과 Propofol 정맥주사시에발생하는통증을완화시켜줄목적으로소량의 ketamine 사용후 propofol 을정주하는방법도효과적이다. 27 또한, midazolam+fentanyl 의사용도빠른유도시간과비교적짧은지속시간으로효과적인방법으로알려져있다. 1578명을대상으로시행한연구에서심각한무호흡이발생한경우는 2예이며 20초이상산소포화도가 92% 이상감소한경우는 0.7% 이고다른심각한부작용없이성공적인시술이수행되었다고보고되었다. 30 Ketamine 과다른약제의조합도사용될수있지만연구가부족하며특히, 이를이용한상부위장관내시경시일부에서후두연축이보고되어주의하여사용되어야한다. 31 약제를투여할경우소아의체중에근거해서용량을결정해야하며, 소아진정내시경을시행할경우의식하진정상태에서도저산소증이발생할가능성이높으므로산소투여는필수적이다. 4. 전신질환이있는환자에서의진정내시경 1) 만성간질환대부분의진정요법에사용되는약제가간으로대사되고있으나아직까지중증간질환을가진환자에대한진정요법에대한권장지침은미미한사항이다. 간질환은간혈류량의변화, 문맥전신순환연결 (portosystemic shunt), 단백질합성, 약제대사과정에심각한영향을미친다. 31 이런변화는진정제의약물동력학에큰영향을줄수있다. 그외진정약제에대한신경민감도의증가, 기존의초기간성혼수, 신장기능장애, 알코올이나약물오남용등도문제가된다. 반감기가짧은 Fentanyl 이간경변증에서흔히사용되며, Propofol 은혈액 뇌장벽을쉽게투과하여발현이빠르고작용시간이짧아, 간에서대사가주로이루어짐에도불구하고간질환의정도나다른신장질환, 비만등에따른용량조절이없이사용할수있다. 진정요법에사용되는 meperidine 은간에서대사되어비활동성 meperidinic acid나 normeperidine 으로분해된다. 이는진통작용을가지고있으며반감기가길고경련, 환각과같은독성작용을가진다. Normeperidine 은신장기능에장애가있으면체내축적되어마약성약제의수용체길항체인해독제를투여하여도 normeperidine 의부작용을치료하기어렵다. 따라서 meperidine은중증간질환을가진환자에게권장되지는않는다. 32 2) 호흡기질환만성폐쇄성폐질환, 폐기종, 간질성폐질환등은만성호흡부전을유발하는질환으로진정수면요법으로인한합병증이증 제 50 회대한소화기내시경학회세미나 287

4 가될수있다. 현재까지내시경이가능한강제호기량 (Forced expiratory volume, FEV1) 및강제폐활량 (Forced vital capacity, FVC) 에대한기준은없으며, 안정상태에서호흡곤란이없고산소포화도가 90% 이상유지되며폐심장증 (Cor pulmonale) 과같은심한장애가동반되어있지않다면진단적내시경검사를시행하는것이가능하다. 그렇지만, 호흡기질환으로 24 48시간이내에사망이예측되거나심한호흡부전을보이는환자는내시경시술을회피하는것이좋다. 33 결론 내시경시행이증가됨에따라다양한환자에서진정이이루어지고있으며, 각환자에따른위험도및평가가우선되어야한다. 고령환자, 임산부, 소아, 만성호흡기및간질환환자에서각각최적의진정방법이다르고, 고려해야할사항이다르므로각상황에맞는진정방법과준비과정을잘이해한다면여러경우에있어서도진정내시경은대부분안전하게시행될수있을것이다. 이를통하여환자에게는안전하면서불안감을해소시키고, 불편감을덜어주면서또한, 시술자에게는충분히만족할만한환경을조성하여완벽한검사또는시술이이루어지도록할수있으리라생각된다. 참고문헌 1. American Society of Anesthesiologists Task Force on Sedation and Analgesia by Non Anesthesiologists. Practice guidelines for sedation and analgesia by non anesthesiologists. Anesthesiology 2002;96: Day LW, WalterLC, Velayos F. Colorectal cancer screening and surveillance in the elderly patient. Am J Gastroenterol 2011;106: ASGE Standards of Practice Committee. Modifications in endoscopic practice for the elderly. Gastrointest Endosc 2013; 78(1): Lukens FJ, Loeb DS, Machicao VI, et al. Colonoscopy in octogenarians: a prospective outpatient study. Am J Gastroenterol 2002;97: Boss GR, Seegmiller JE. Age related physiological changes and their clinical significance. West J Med 1981;135: Shaker R, Ren J, Bardan E, et al. Pharyngoglottal closure reflex: characterization in healthy young, elderly and dysphagic patients with predeglutitive aspiration. Gerontology 2003;49: Muravchick S. Anesthesia for the geriatric patient. Curr Opin Anaesthesiol 2002;15: Peacock JE, Lewis RP, Reilly CS, et al. Effect of different rates of infusion of propofol for induction of anaesthesia in elderly patients. Br J Anaesth 1990;65: Darling E. Practical considerations in sedating the elderly. Crit Care Nurs Clin North Am 1997;9: Cohen LB, Hightower CD, Wood DA, et al. Moderate level sedation during endoscopy: a prospective study using low dose propofol, meperidine/fentanyl, and midazolam. Gastrointest Endosc 2004;59: Heuss LT, Schnieper P, Drewe J, et al. Conscious sedation with propofol in elderly patients: a prospective evaluation. Aliment Pharmacol Ther 2003;17: Horiuchi A, Nakayama Y, Tanaka N, et al. Propofol sedation for endoscopic procedures in patients 90 years of age and older. Digestion 2008;78: Hayee B, Dunn J, Loganayagam A, et al. Midazolam with meperidine or fentanyl for colonoscopy: results of a randomized trial. Gastrointest Endosc 2009;69: Qureshi WA, Rajan E, Adler DG, et al. ASGE Guideline: Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc 2005;61(3): ASGE Standard of Practice Committee. Guidelines for endoscopy in pregnant and lactating women. Gastrointest Endosc 2012;76(1): Cappell MS. Risk versus benefits of gastrointestinal endoscopy during pregnancy. Nat Rev Gastroenterol Hepatol 2011;8: Gin T. Propofol during pregnancy. Acta Anaesthesiol Sin 1994; 32: Physician s desk reference. 56th ed. Montvale (NJ): Medical Economics Co; Dolovich LR, Addis A, Vaillancourt JMR, et al. Benzodiazepine use in pregnancy and major malformations or oral cleft: metaanalysis of cohort and case controlled studies. BMJ 1998;317: Laegreid L, Olegard R, Wahlstrom J, et al. Teratogenic effects of benzodiazepine use during pregnancy. J Pediatr 1989;114: Cappell MS. The fetal safety and clinical efficacy of gastrointestinal endoscopy during pregnancy. Gastroenterol Clin North Am 2003;32: Heinonen OP, Stone D, Shapiro S. Birth defects and drugs in pregnancy. Boston: John Wright; Cunningham FG, Gant NF, Leveno KJ. Analgesia and sedation. In: William s Obstetrics, 21st ed, New York: McGraw Hill; p Nitsun MJ, Szokol JW, Saleh HJ, et al. Pharmacokinetics of midazolam, propofol, and fentanyl transfer to human breast milk. Clin Pharmacol Ther 2006;79: American Academy on Pediatrics; American Academy on Pediatric Dentistry. Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures: an update. Paediatr Anaesth 2008;18(1): American Academy on Pediatrics; American Academy on Pediatric Dentistry. Guidelines for monitoring and management of pediatric patients during and after sedation for diag- 288 Korean Society of Gastrointestinal Endoscopy

5 nostic and therapeutic procedures: an update. Pediatrics 2006;118(6): van Beek EJ, Leroy PL. Safe and effective procedural sedation for gastrointestinal endoscopy in children. J Pediatr Gastroenterol Nutr 2012;54(2): Powers KS, Nazarian EB, Tapyrik SA, et al. Bispectral index as a guide for titration of propofol during procedural sedation among children. Pediatrics 2005;115: Barbi E, Petaros P, Badina L, et al. Deep sedation with propofol for upper gastrointestinal endoscopy in children, administered by specially trained pediatricians: a prospective case series with emphasis on side effects. Endoscopy 2006;38: Mamula P, Markowitz JE, Neiswender K, et al. Safety of intravenous midazolam and fentanyl for pediatric GI endoscopy: prospective study of 1578 endoscopies. Gastrointest Endosc 2007;65: Green SM, Klooster M, Harris T, et al. Ketamine sedation for pediatric gastroenterology procedures. J Pediatr Gastroenterol Nutr 2001;32: Bamji N, Cohen LB. Endoscopic sedation of patients with chronic liver disease. Clin Liver Dis 2010;14(2): Thuluvath PJ. Toward safer sedation in patients with cirrhosis: have we done enough? Gastrointest Endosc 2009;70: 이완식. 만성질환환자에서의안전한내시경검사. Korean J Gastrointest Endosc 2009;38(Suppl 1): 제 50 회대한소화기내시경학회세미나 289

E-III 진정 : 더높은곳을향하여 E Room 새로운진정약물소개 : Fentanyl, Etomidate, Ketamine, Dexmedetomidine, Remimazolam 등 장동기 동국대학교의과대학동국대학교일산병원내과학교실 Novel Agents for Seda

E-III 진정 : 더높은곳을향하여 E Room 새로운진정약물소개 : Fentanyl, Etomidate, Ketamine, Dexmedetomidine, Remimazolam 등 동국대학교의과대학동국대학교일산병원내과학교실 Novel Agents for Sedative Endoscopy: Fentanyl, Etomidate, Ketamine, Dexmedetomidine