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1 대한내과학회지 : 제 82 권제 5 호 특집 (Special Review) - 구역과구토 (nausea and vomiting) 수술후구역과구토 연세대학교의과대학내과학교실 임현철 Postoperative Nausea and Vomiting Hyun Chul Lim Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea Postoperative nausea and vomiting (PONV) is considered as a main cause of dissatisfaction after surgery with postoperative pain. Overall incidence of PONV is 30%, and the incidence rate can increase up to 70-80% in high-risk patient groups. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, surgical procedure, and anaesthetic technique. Pharmacological treatments including dopamine antagonist, anti-histamines, anticholinergics, dexamethasone, neurokinin-1, and serotonin antagonist are used to prevent and treat PONV. This article reviews the prevalence, mechanisms, and risk factors of PONV, and how to prevent and treat it. (Korean J Med 2012;82: ) Keywords: Postoperative nausea and vomiting 서 론 위험인자, 기전및예방과관리에대하여기술하고자한다. 수술후구역과구토 (postoperative nausea and vomiting, PONV) 는수술후통증과함께환자들에게발생하는가장흔한합병증이다. 수술후구역과구토를줄이기위한노력이현재까지계속시도되고있지만, 아직까지도 22-28% 환자에서구역이 12-26% 의환자에서구토증상이발생한다. 수술후구역과구토는환자에게고통을주며, 회복기간과입원기간을연장시켜환자의만족도를떨어트리고의학적비용을증가시키는중요한원인으로작용하고있다 [1,2]. 본종설에서는최근까지알려진수술후구역과구토의 본론수술후구역과구토의발생률서구선진국의경우 2000년이후약 100명당 명의빈도에서수술이시행되고있으며, 특히미국의경우매년 7,100만명이상이마취를동반한수술을시행받고있다 [3,4]. 수술후구역과구토의경우일반적으로예방적조치를하지않는경우약 30% 정도의환자에서나타나며, 위험인자를가지고있는경우그발생률이약 70-80% 까지증가 Correspondence to Hyun Chul Lim, M.D. Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 225 Geumhak-ro, Cheoin-gu, Yongin , Korea Tel: , Fax: , mdlhc@daum.net

2 - The Korean Journal of Medicine: Vol. 82, No. 5, 한다. 수술후구역과구토는의식이있는환자에게위협적인증상은아니지만, 지속적으로발생할경우탈수와저칼륨혈증, 대사성알칼리혈증과같은전해질불균형을유발할수있다. 또한구역과구토시발생하는체내압력의변화는시력의소실, 상처의회복지연, 식도파열, 혈종의발생등의합병증을유발할수있다. 특히마취에서완전히깨어나지못한상태에서발생하는구역과구토의경우흡입성폐렴등을포함한폐질환등생명을위협할수있는심각한합병증을유발할수있다. 수술후구역과구토의기전과병태생리현재까지연구에의하면구역을유발하는외부적자극 ( 통증, 감정, 성격등 ) 이구심신경을통하여뇌간에위치한구토중추와대뇌피질에영향을주어구역과구토를발생시킨다고한다. 또한위장에서의미주신경의자극및혈액-뇌장벽밖에위치하는화학수용체유발영역 (chemoreceptor trigger zone, CTZ) 의구심성자극이뇌의맨아래구역 (area postrema) 과구역중추에작용하여구토를유발하는것으로알려져있다. 뇌의맨아래구역에는아편유사물체수용체, 도파민 D 2 수용체, 세로토닌수용체의농도가높고, 화학수용체유발영 Table 1. Risk factors for postoperative nausea and vomiting Strong positive Female gender History of motion sickness or PONV Postoperative opioids Non-smoking status Mostly positive Young age and physical status Nitrous oxide Muscle relaxant General versus regional anesthesia Volatile anesthetics Conflicting Site of surgery Menstrual cycle Experience of the anaesthetist Gastric tube for decompression of the stomach Insufficient data Pain Anxiety and personality PONV, postoperative nausea and vomiting. 역에는아편유사물체수용체, 도파민 D 2 수용체, 엔케팔린 (enkephalin) 의농도가높으며, 이러한신경수용체영역은약물, 전해질이상이나대사이상등의자극에의해구토반사를일으키게된다. 대부분의항구토제는화학수용체유발영역의수용체에직간접적으로작용한다. 수술후구역과구토의발생에는다양한수용체가관여하므로, 단일약제보다는다른수용체에작용하는여러약제들을조합하여사용하는것이고용량의단일약제사용에따른부작용을줄일수있으며, 증상의예방과치료에좀더효과적이다 [5,6]. 수술후구역과구토의위험인자 수술후구역과구토발생의위험인자에대하여많은연구들이진행되고있으며, 위험인자를가진군에서발병률이높게나타나기때문에적극적인처치가필요하다. 현재까지알려진대표적인위험인자로는여성, 이전수술후구역과구토또는멀미의병력, 비흡연상태, 수술후아편계약물사용이다 (Table 1) [7]. 위험인자들은수술후구역과구토의발생률을독립적으로증가시키며, 위험인자가한가지씩많아질수록수술후구역과구토의발생률은 8-20% 씩증가한다 (Table 2) [8]. 수술후구역과구토의마취와관련된위험인자로는흡입제의종류와용량, nitrous oxide의사용, 고용량의근이완제의사용이며, 수술술기와관련하여긴수술시간과복부수술이대표적인요인이다. 위험인자는항구토예방을위한가이드라인으로사용하여고위험군을파악하고적극적인예방을시도할수있으나, 모든환자에게동일하게적용하기에는어려움이있다. Table 2. Risk of postoperative nausea and vomiting depending on the total score of risk factors Risks of postoperative nausea and Total score of risk factor vomiting a 0 10% 1 20% 2 40% 3 60% 4 80% a Risk factors of postoperative nausea and vomiting: Female gender, History of motion sickness or PONV, Postoperative opioids, Non-smoking status

3 - Hyun Chul Lim. Postoperative nausea and vomiting - 수술후구역과구토의예방과관리비약물적방법수술전환자의불안을줄이는것이수술후구역과구토를감소할수있는중요한요인으로, 환자에게정확한정보를주고의료진과의교감을쌓는것이예방에중요하다 [9,10]. 또한수술전후에충분한탄수화물의공급및적극적인수액공급역시예방적인효과를볼수있다 [11,12]. 부분마취가전신마취에비하여수술후구역과구토를줄이고, 수술중에는흡입마취제 ( 특히 nitrous oxide) 의사용을최소화하고, 정맥투여를통한마취 ( 특히 propofol) 가수술후구역과구토를줄일수있다 [13]. 아편계진통제는수술중마취에서중요한부분을차지하지만, 수술후구역과구토를증가시킬수있다 [14]. 통증자체도수술후구역과구토를유발할수있으므로아편계진통제의적절한사용이필요하지만, 최근에는수술후통증을조절하기위한사용을줄이기위하여비스테로이드성항염증제 (non-steroidal anti-inflammatory drugs, NSAIDs) 의복합사용이수술후구역과구토의예방을위하여사용할수있다 [15,16]. 침술도수술후구역과구토를예방하는데사용할수있으며, 임산부에게시술시약 30% 까지증상을감소시키는것으로보고되고있다 [17,18]. 약물적치료법수술후구역과구토를줄이기위한약제는수용체에작용하는종류에따라서분류할수있고대부분미주신경의말초부위또는최하위부분에작용하며, 도파민길항제, 항히스타민제, 항콜린성제, 스테로이드제, 세로토닌수용체억제제, NK 1 길항제등이주로사용되고있다 (Table 3) [19]. 도파민길항제 Metoclopramide 는수술후구역과구토의예방에가장흔히사용되는도파민길항제 (benzamides 계 ) 로, 중추및말초의도파민 D 2 수용체에작용한다. 고용량의사용은추체외로증상을유발할수있기때문에수술후구역과구토예방을위하여 mg이주로사용되고있다 [20]. Droperidol은중추의도파민 D 2 길항제 (butyrophenone 계 ) 약제로수술후구토와구역을억제하는약제로사용되며, 3시간이내의짧은작용시간을가지고있어수술이끝날때 투여하는것을권장한다. 일부환자에서부정맥이나타날수있으므로사용후 3시간동안은심전도모니터링을필요로한다 [21]. Haloperidol 역시도파민 D 2 길항제 (butyrophenone 계 ) 로수술후구역과구토를억제하는효과가있으나, 부정맥발생을유발할수있어주의를요하며, 특히미국에서는정맥정주보다는근육점주에만사용이허가되어있다. 부정맥의부작용이나타나는환자들은보통 herg (Human ether-á-go-go related gene) 를전사하는부분의돌연변이를가진군에서 QT 간격의연장을유발하기때문에실제로예측하기는어려운것으로알려져있다 [22]. 항히스타민제수술후구역과구토에주로사용되는항히스타민제는 diphenhydramine, dimenhydrinate, cyclizine, promethazine이있다. 이약제들은화학수용체유발영역보다는고속핵 (nucleus tractus solitarius) 의히스타민 H 1 수용체에작용하는것으로알려져있다 [23]. 항히스타민은진정효과의부작용이있기때문에수술이마치기직전에주면회복시간을지연시킬수있으므로주의를요한다 [19]. 항히스타민제의효과는아직까지제한적이며, 다른약제에비하여연구가부족한실정이다. 항콜린성제 Atropine과 scopolamine은대뇌피질과뇌교에분포하는무스카린수용체를억제하여수술후구역과구토를줄여주는것으로알려져있다. Atropine의효과는현재까지논란이있으나 scopolamine은수술후구역과구토를효과적으로억제하는것으로알려져있다. Scopolamine의경피투여는약의짧은반감기를극복하고약동학적으로효과적으로작용할수있게해주는방법으로수술후 24시간이내의구역과구토를줄일수있는것으로알려져있으며, 부작용으로는구강건조, 위장기능의감소, 동공산대, 어지러움, 심박동수의증가가알려져있다 [24]. 스테로이드제 Dexamethasone은예전부터항암치료에따른구역과구토의치료에사용되어왔다. 작용기전은아직까지명확하지않으나, 동물모델에의하면고속핵의억제에직접적으로작용한다고한다. 현재추천용량은마취유도시에 5 mg을투

4 - 대한내과학회지 : 제 82 권제 5 호통권제 621 호 Table 3. Antiemetic drugs with efficacy in the prevention of postoperative nausea and vomiting Name Class of drug Fixed dose Metoclopramide Dopamine (D 2), benzamides Droperidol Dopamine (D 2), butyrophenones Haloperidol Dopamine (D 2), butyrophenones Dimenhydrinate Histamine (H 1) antagonist Scopolamine Anticholinergic agents (antagonist at muscarinic acetylcholine receptors) Recommended time of administration mg Late (towards the end of anaesthesia) mg Late (towards the end of anaesthesia) mg 62 mg Late (towards the end of anaesthesin Transdermal therapeutic system Early (the day before surgery or prior to induction of anaesthesia) Adverse effects Extrapyramidal disturbances, hypotension Psychomimetic side-effects, extrapyramidal disturbances, Sedation Dizziness, dry mouth, visual disturbances Dexamethasone Corticosteroid 4-8 mg Early (at induction) Increased blood glucose, hypotension/hypertension; Granisetron Serotonin (5-HT 3) Ondansetron Serotonin (5-HT 3) Palonosetron Serotonin (5-HT 3) Tropisetron Serotonin (5-HT 3) Aprepitant Neurokinin (NK 1 receptor ) 5-HT 3, 5-hydroxytryptamine receptor. 1 mg Late (towards the end of anaesthesia) 4 mg mg 2 mg 40 mg Early (prior to surgery on the day of surgery) Headache, constipation, raised liver enzymes; Headache, constipation Absolute or relative contraindications Parkinson's disease Parkinson's disease, prolonged QT-interval Diabetes mellitus (relative) Prolonged QT-interval 여하면예방효과를볼수있다고한다 [25]. 세로토닌수용체억제제 (5-HT 3 수용체길항제 ) 세로토닌수용체억제제는수술후구역과구토예방에현재가장흔하게사용되고있다 [26]. 세로토닌은구역발생에중요한역할을하며 5-HT 3 는수용체의자극은화학수용체유발영역과미주신경말단에작용하여구역을일으키는것으로알려져있다 [27]. Ondansetron, dolasetron, granisetron과 palonosetron 같은항구역제는선택적인 5-HT 3 수용체길항제로모두효과는비슷하게나타나고, 두통및장운동장애등의부작용이있다. 가장흔하게사용되는약제들이지만이들은 QT 기간연장과부정맥 (torsade de pointes) 을유발하여심장마비를일으 킬수있다. Palonosetron은가장최근에개발된세로토닌길항제로아직까지 QT 연장에영향을주지않으며 mg의저용량으로도수술후 72시간동안구역과구토를예방하는것으로보고되고있다 [28]. Neurokinin-1 수용체길항제 Substance P는 neurokinin-1 (NK 1) 수용체의작용을억제하여고속핵에서신경전달을감소시킴으로써수술후구역과구토를예방한다. FDA에서승인받은첫번째 NK 1 수용체길항제는 aprepitant으로임상연구에서효과적인수술후구역과구토예방효과를나타내었다 [29]. 최근에추가적으로 rolapitant과 casopitant가연구중에있으나아직까지 FDA 승인을받지못하였다. NK 1 수용체억제제는항히스타민제같

5 - 임현철. 수술후구역과구토 - 은진정작용이없으며, 세로토닌수용체억제제에서발생하는 QT 연장도나타나지않는다고보고되고있다. 아편계길항제아편계약물은구역과구토를유발할수있는중요한요인이므로, 사용량을줄이기위하여 NSAIDs 병용사용을추천하며, μ-opioid 수용체길항제 (naloxone, alvimopan) 등을시도해볼수있다. 하지만아편계길항제에대한임상적인연구들이더필요한실정이다. 결 지난수십년간수술후구역과구토를줄이기위한수많은연구들이진행되어왔다. 수술후구역과구토의발생은여러가지원인에의하여발생하기때문에완벽하게해결하는것은매우어려운문제이며, 수술후구역과구토를줄이기위해서는위험요소의평가, 위험인자에따른예방과치료를모두포함하는체계적인접근이필요하다. 다양한연구들을통하여향후구역과구토발생을최소화하여환자의만족도를높이고의료비용을줄이려는노력이계속되어야한다. 론 중심단어 : 수술후구역과구토 REFERENCES 1. Franck M, Radtke FM, Apfel CC, et al. Documentation of postoperative nausea and vomiting in routine clinical practice. J Int Med Res 2010;38: Cohen MM, Duncan PG, DeBoer DP, Tweed WA. The postoperative interview: assessing risk factors for nausea and vomiting. Anesth Analg 1994;78: Clergue F, Auroy Y, Pequignot F, Jougla E, Lienhart A, Laxenaire MC. French survey of anesthesia in Anesthesiology 1996;91: Owings MF, Kozak LJ. Ambulatory and inpatient procedures in the United States, Vital Health Stat 1998;13: Cosow CE, Haspel KL, Smith SE, Grecu L, Bittner EA. Haloperidol versus ondansetron for prophylaxis of postoperative nausea and vomiting. Anesth Analg 2008;106: Fujii Y, Itakura M. A prospective, randomized, doubleblind, placebo-controlled study to assess the antiemetic effects of midazolam on postoperative nausea and vomiting in women undergoing laparoscopic gynecologic surgery. Clin Ther 2005;32: Apfel CC, Laara E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology 1999;91: Kreis ME. Postoperative nausea and vomiting, Auton Neurosci 2006;30;129: White PF. Prevention of postoperative nausea and vomitinga multimodal solution to a persistent problem. N Engl J Med 2004;350: Jung JS, Park JS, Kim SO, et al. Prophylactic antiemetic effect of midazolam after middle ear surgery. Otolaryngol Head Neck Surg 2007;137: Jensen K, Kehlet H, Lund CM. Post-operative recovery profile after laparoscopic cholecystectomy: a prospective, observational study of a multimodal anaesthetic regime. Acta Anaesthesiol Scand 2007;51: Scuderi PE, James RL, Harris L, Mims GR III. Multimodal antiemetic management prevents early postoperative vomiting after outpatient laparoscopy. Anesth Analg 2000; 91: Joo HS, Perks WJ. Sevoflurane versus propofol for anesthetic induction: a meta-analysis. Anesth Analg 2000; 91: Roberts GW, Bekker TB, Carlsen HH, Moffatt CH, Slattery PJ, McClure AF. Postoperative nausea and vomiting are strongly influenced by postoperative opioid use in a dose-related manner. Anesth Analg 2005;101: Shende D, Das K. Comparative effects of intravenous ketorolac and pethidine on perioperative analgesia and postoperative nausea and vomiting (PONV) for paediatric strabismus surgery. Acta Anaesthesiol Scand 1999;43: Marret E, Kurdi O, Zufferey P, Bonnet F. Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology 2005;102: Fan CF, Tanhui E, Joshi S, Trivedi S, Hong Y, Shevde K. Acupressure treatment for prevention of postoperative nausea and vomiting. Anesth Analg 1997;84: Zarate E, Mingus M, White PF, et al. The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery. Anesth Analg 2001;92: Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev 2006;CD Wallenborn J, Gelbrich G, Bulst D, et al. Prevention of

6 - The Korean Journal of Medicine: Vol. 82, No. 5, postoperative nausea and vomiting by metoclopramide combined with dexamethasone: randomised double blind multicentre trial. BMJ 2006;333: White PF. Droperidol: a cost-effective antiemetic for over thirty years. Anesth Analg 2002;95: Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug induced QT prolongation and life threatening arrhythmias. J Cardiovasc Electrophysiol 2000;11: Scuderi PE. Pharmacology of antiemetics. Int Anesthesiol Clin 2003;41: Apfel CC, Zhang K, George E, et al. Transdermal scopolamine for the prevention of postoperative nausea and vomiting: a systematic review and meta-analysis. Clin Ther 2010;32: Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350: Gyermek L. 5-HT 3 receptors: pharmacologic and therapeutic aspects. J Clin Pharmacol 1995;35: Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992;77: Kovac AL, Eberhart L, Kotarski J, et al. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour period. Anesth Analg 2008;107: Diemunsch P, Gan TJ, Philip BK, et al. Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery. Br J Anaesth 2007;99:

충북의대학술지 Chungbuk Med. J. Vol. 27. No. 1. 1~ Charcot-Marie-Tooth Disease 환자의마취 : 증례보고 신일동 1, 이진희 1, 박상희 1,2 * 책임저자 : 박상희, 충북청주시서원구충대로 1 번지, 충북대학교

충북의대학술지 Chungbuk Med. J. Vol. 27. No. 1. 1~5 2017 Charcot-Marie-Tooth Disease 환자의마취 : 증례보고 신일동 1, 이진희 1, 박상희 1,2 * 책임저자 : 박상희, 충북청주시서원구충대로 1 번지, 충북대학교의과대학마취통증의학교실, 의학연구소 (28644), happycat19@hanmail.net