대한내과학회지 : 제 82 권제 5 호 2012 http://dx.doi.org/10.3904/kjm.2012.82.5.525 특집 (Special Review) - 구역과구토 (nausea and vomiting) 임신중구역과구토의관리 영남대학교의과대학내과학교실 김경옥 Nausea and Vomiting in Pregnancy Kyeong Ok Kim Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea Nausea and vomiting in pregnancy (NVP) is common medical condition during pregnancy and associated with hormonal change. Early recognition and active treatment is warranted because it can be associated with adverse healthy effect in both fetus and mother. First, the possibility of other gastrointestinal disorder should be considered and precipitating factor, renal and liver function should be evaluated. Primay recommended pharmacotherapy is the combination of oral pyridoxine hydrochloride and doxylamine succinate. Other options including dopamin (D2) receptor antagonist, antihistamine and serotonine 5 hydroxytryptamine 3-receptor (5-HT3) can be used. Fluid mixed with multivitamine including thiamine supplement should be considered in case of severe dehydration and hyperemesis gravidarum. Emotional support is also an important part in the management of NVP. The physician shoud apply individualized approach for the safest and most appripriate treatment. (Korean J Med 2012;82:525-531) Keywords: Nausea and vomiting, pregnancy; Hyperemesis gravidarum; Therapy 서론구역및구토는임신중비교적흔하면서치료가쉽지는않은증상들로임신초기여성의 50% 에서보고된다 [1]. 증상이경미하여보존적치료로호전되는경우에서부터경과가심하고오래지속되어다각적접근및입원치료를요하는임신오조 (hyperemisis gravidarum) 까지다양한경과를보일수있다 [2-4]. 초기에적절한치료를해야하겠지만환자와의사간의의사소통이제대로되지않아증상이심해지는 경우가드물지않다. 실제임신중구역및구토는충분히치료가되지않는경우가많으며, 약제에대한안전성이나유효성에대한연구가충분하지않다. 임신중비교적흔한증상이지만이로인해임산부의삶의질이저하되며, 심할경우탈수및체중감소가발생하며태아에게도좋지않은영향을미치므로충분한고찰과적극적인치료가필요할것이다. 이에본고에서는임신중구역및구토의원인, 증상과약물및비약물적치료에대해서알아보고자한다. Correspondence to Kyeong Ok Kim, M.D. Department of Internal Medicine, Yeungnam University Medical Center, 170 Hyeonchung-ro, Nam-gu, Daegu 705-717, Korea Tel: +82-53-620-4197, Fax: +82-53-654-8386, E-mail: cello7727@naver.com - 525 -
- The Korean Journal of Medicine: Vol. 82, No. 5, 2012 - 본론원인및위험인자임신중구역및구토는대개임신의 50-90% 정도로보고되고있으며이중 50-55% 정도는두가지증상을모두동반하고있으며 25% 정도는구역증상만을호소한다 [2-4]. 임신 4-9주경부터증상이시작되어 12-15주경가장심하고 20주가되면대부분호전되는경과를취하게되지만 9-20% 정도의임산부는 20주가넘거나심한경우임신기간내내지속되는경우도있다 [4-6]. 임신오조는임신중구역및구토의심한형태로 0.3-3% 에서발생하게되며증상이매우심하고, 지속되어체중감소, 탈수및전해질이상, 티아민등의비타민및미량원소결핍등이초래되는상태로정의가된다 [5,7-9]. 이것은임신중발생하는 hcg, 에스트로겐, 프로게스테론및갑상선호르몬농도의변화가임신초기에가장흔하여이로인해발생한다는의견이가장흔하다 [10]. 실제한연구에의하면대조군에비해임신오조환자군에서 hcg 농도가유의하게높았고, 이는실제임신오조의발생이영양막 (trophoblast) 이가장활동적으로 hcg를생산할때높았다는연구에의해지지되었다 [10]. 뿐만아니라 hcg가갑상선자극호르몬 (thyroid stimulating hormone) 과구조적으로유사해서임신오조환자들대부분은갑상선기능이상소견을보이기도한다. 임신중소화기에서생리적인변화가현격하게보일수있는데위운동이상이나위신경활동이상소견등이있고이러한현상은에스트로젠이나프로게스테론에의한것이며 [11], 자궁의확장및복강내장기의위치변경으로인해역류및구역구토가발생하게되는데이러한증상은기저에당뇨성위병증이나위식도역류질환, 염증성장질환등이있을경우더저명하게나타나게된다 [11,12]. 만약산모가이전에이러한소화기문제가있다면치료는이러한상황에맞춰시행되어야할것이다. 그외에도헬리코박터양성률이대조군에비해임신중구역및구토가있는산모에서유의하게높았다는보고도있으며, 유전적인요소가연관이있어실제심한증상을보이는환자의상당수가모친이나여자형제에서비슷한증상을보였다는연구도있다 [13,14]. 알려진위험인자로는가족력, 다산력, 포상기태, 젊은연령등이있으며 [15], 스트레스, 수면부족, 만성적헬리코박터 감염, 소화성궤양, 편두통등이그증상을악화시킨다 [16,17]. 증상및진단 개인마다차이가있겠지만주된증상으로는오심, 구역, 구토및음식에대한혐오등이있으며개개인마다증상이심해지는요인이있다 [18-20]. 병력청취를통해증상의시작시기, 심한정도, 악화및호전인자등을통해다른원인의가능성을감별해야하며임신과관련된구역및구토라고진단을하기전에반드시비임신적인원인은아닌지감별해볼필요가있는데대개 10주이전에증상이발생했다면그것은임신과관련될가능성이크지만증상이비전형적이거나, 치료에반응을하지않거나, 10주이후에첫증상이발생하였다면다음과같은질환들을감별해볼필요가있다 [3,5,7] (Table 1). 일단진단이되면소변케톤, 간및신장기능, 전해질상태및갑상선기능을파악해두고 Pregnancy-Unique Quantification of Emesis Scale (PUQE) 라는점수법을이용하여증상의정도를평가한다 [21-23]. 이것은주로임신중발생하는오심및구토에초점을두고고안된것으로최소 3점부터 15점까지있고, 6점이하의경우경증, 7-12점의경우중등도, 13점이상의경우중증으로타당성이확인되었으며입원이나개인의주관적느낌과잘연관되는것으로알려져있고, 증상평 Table 1. Differential diagnosis of nausea and vomiting in pregnancy Gastroenteritis Peptic ulcer Gastroesophageal reflux disease Acute fatty liver of pregnancy Cholecystitis Pancreatitis Appendicitis Helicobacter pylori infection Pyelonephritis Urinary tract infection Preeclampsia Central nervous system abnormality Hyperthyroidism - 526 -
- Kyeong Ok Kim. Nausea and vomiting in pregnancy - 가뿐아니라치료에대한반응을평가하는데도도움이되겠다 [24]. 비약물치료우선적으로증상을발생시킬만한음식이나냄새등을피하도록해야하는데흔히증상을발생시키는것들로는기름기있는음식이나자극적음식, 철분제등이있고, 소량씩자주먹도록하며식사중간에수분섭취를하는것이도움이된다 [25]. 전통적으로아침에크레커등을먹어공복을피할것을권유하였지만실제무작위연구에서단백질위주의식사가구역증상을오히려더감소시켰다고보고하였다 [26]. 두가지비약물적접근이증상에도움이된다고알려져있는데이들은주로경한증상에서약물치료를원치않는환자에서이용된다. 비약물적치료전환자에게먼저약물이필요한경우약물치료를하지않는것은오히려더해가될수있다는것을충분히설명할필요가있다 [18]. 두가지비약물치료가근거가있는데, 생강을 250 mg씩 4회복용하였을때효과가있었다는보고가있지만안정성에관한자료는충분하지는않다 [27]. 그밖에 P6에침을이용해자극할경우지속적인구역을감소시킨다는보고가있다 [28,29]. 증상의정도가심하지않더라도탈수의징후가보이면 crystalloid 정맥수액치료가도움이된다. 최근에는많은병원들이외래에서수액치료가가능하도록하여주기적으로증상이심할때마다내원하여치료받을수있도록하고있다. 임신오조의경우수액및항구토제등의다양한접근이필요하며, Wernickes 뇌증등이발생하지않도록티아민을포함한비타민공급이함께이루어져야한다 [30]. 약물적치료습관변화나영양적지지에도불구하고증상호전을위해약물치료가필요한여성은약 10% 정도로보고되고있다 [30]. 미국산부인과학회에서는 pyridoxin 단독치료에반응이없는경우경구 pyridoxin hydrochloride (vit B6) 와 doxylamine succinate 가효과및안정성에서가장좋으므로일차치료로이용할것을권고하고있다 [5]. Pyridoxine은수용성비타민으로아미노산, 지질및탄수화물의대사에관여하며, doxylamine은 1 수용체에서직접적으로히스타민을억제하는작용을하며, 간접적으로전정기관에작용하며, 무스카린수용체에억제작용을보여구토중추의자극을감소시키게 된다 [31-33]. 각각을단독으로복용할수있지만최근캐나다에서하나의제제로복합한약제가나왔다 [33]. Pyridoxin과 doxylamine의병합치료는대부분의연구에서임신초기를포함한임신기간중안전하고효과적인것으로보고되었다 [5,7]. 아침에증상이가장심하지만하루종일지속적인증상이있는경우취침전 2정, 아침에 1정으로오후증상을조절하고, 오후에 1정으로저녁증상을조절할수있으며, 증상이호전되고나서는서서히줄이는것이재발이적다. 돌발성구역및구토에대해서는다른계통의항히스타민제제나도파민길항제등으로치료할수있다. Dimenhydrinate 는히스타민 1 수용체길항제로임신중구역및구토에널리이용되며여기에구토로인한역류혹은작열감과관련된증상이있는경우히스타민 2 수용체도그안정성이나효과면에서근거가있는약제가되겠다 [34]. 도파민길항제로는도파민2 (D2) 수용체길항제인 phenothiazine이화학수용체유발중추를억제하며, 위장관에위치하는 D2 수용체를통해위의운동성을저하시켜항구역효과를보이면서동물및인간실험에서임신초기기형의위험을증가시키지는않는것으로되어있다 [32,33]. Metoclopramide도도파민수용체길항제로안정성및효용성에대한연구가충분하지않음에도불구유럽을비롯하여널리이용되는것으로이것은위장관통과시간을감소시키면서화학수용체유발중추에작용하여항구역효과뿐아니라소화관운동촉진제의역할까지가지고있다 [30,33,35]. 이론적으로위저류가증상의기저에동반된임산부에게이용하면도움이된다 [18]. Domperidone 이나 Droperidol은심한증상에서고려해볼수있겠지만데이터가충분하지않으며 trimethobenzamide는안전하고효과적인것으로알려져있다 [18]. 세로토닌 3 (5-HT3) 수용체는원래항암제와관련된구역및구토의 1차약제로고려되지만 ondansetron의경우임신중구역및구토나임신오조에서널리이용되고있다. 미국산부인과진료지침에서 5-HT3 길항제는 3차약제로권고하지만실제 ondansetron은 phenothiazine보다진정작용이적어비교적일찍사용하고있다 [5]. 임신중사용에대한데이터가충분하지는않지만인간에서보다더많은용량을사용한동물실험에서임신 1기에사용하였을때기형발생의증거는없었으며, 임신 1기에 ondansetron에노출된 169명의영아를대상으로한전향적비교관찰연구에서주요기형발생률이 3.6% 로대조군과유의한차이를보이지않았다 [36,37]. - 527 -
- 대한내과학회지 : 제 82 권제 5 호통권제 621 호 2012 - Table 2. List for pharmacologic treatment of nausea and vomiting during pregnancy Classification Agents FDA category Indication Vitamins Vit B6 A First line choice Cyanocobalamin A Antihistamines Doxylamine A Breakthrough nausea Dimenhydrinate B Diphenhydramine B Dopamine antagonist Promethazines C Second or third line choice Trimethobenzamide C Metoclopramide B 5-HT3 antagonist Ondansetron B After failure to conventional therapy 5-HT3, 5 hydroxytryptamine 3-receptor. 위장관촉진제의경우 cisapride 가기형발생의증거가없다지만데이터가충분하지않으며 [34], 항암제유도구역에서스테로이드의효과에근거하여심한임산부에게스테로이드의사용이제안이되었지만구개열과유의한상관관계가있었고, 효과는미비하여임신 10주전에는사용하지않도록하며사용하더라도다른치료에실패한경우만고려해야겠다 [34]. 양성자펌프억제제의경우초기연구결과가고무적이지만아직은다른치료에실패할경우고려하도록하며삼환계항우울제의경우정동장애가동반된경우고려할수있다 [34,38]. 임신중구역과구토에고려할수있는약제로는다음과같은것이있다 (Table 2). 불응성구역및구토혹은임신오조의치료외래에서약물치료에반응하지않는경우정맥수액및영양지원이필요하다. 구역이지속되더라도비위관경구식이를계속하는것이효과적이다 [39]. 완전비경구영양 (total parenteral nutrition) 은정맥로패혈증, 지방성간염등의위험이있기때문에체중이 5% 이상감소한불응성의환자중경구섭취가되지않는환자에서경구식이가가능할때까지시행되어야한다 [5,16]. 수액치료는처음에는생리식염수로시작하여칼로리를보충해주어야하는데임산부의경우 2,200-2,500 kcal/day가필요하며단백질소실에대해보충이필요하다. 고삼투용액은피하는것이좋으며 5% 농도의용액이적당하겠다. 이때 dextrose가혼합된용액의경우티아민이결핍된환자에서티아민요구량이증가되어 Wernicke s 뇌증이발생할수있으므로티아민보충은비경구영양에 서가장중요한사항이된다. 불응성의경우아미노산이나지방용액을첨가해볼수있다. 심한환자에서는정신적지지도치료의중요한부분이되는데, 배우자뿐아니라다른가족구성원이모두참여할경우더효과적일수있다 [40]. 임산부에게이과정이힘이들지만일시적인것으로분만과함께다호전된다는사실을항상떠올려주고직장에서도좀더편안한스케줄을고려하는것이좋겠다 [41]. 결론임신중구역및구토는복합적이고다인자적인상황으로태아뿐아니라산모의삶의질이나건강에좋지않은결과를초래할수있으므로빨리인지하고치료를할수있도록해야한다. 먼저편두통이나그밖의위장질환의가능성들을먼저고려해야하며, 일단의심이되는환자의경우유발인자를정확하게파악하여야하며신장, 간기능을확인하고전해질및아밀라아제등을평가해야한다. 먼저소량씩자주먹는식습관이도움이될수있으며, pyridoxine과 doxylamine 이무작위연구에서효과가입증이되어일차적인약제로고려될수있겠다. 일차약제에반응하지않는경우 phenothiazine, metoclopramide 등과같은 D2 수용체길항제나, 5 hydroxytryptamine 3-receptor (5-HT3) 인 ondansetron 등이이용될수있고, 구역및구토로인한위장증상및위식도역류증상이동반된경우히스타민 2 수용체가도움이될수있다. 비약물치료로는생강이나침술등이효과가증명이되어있다. - 528 -
- 김경옥. 임신중구역과구토의관리 - Figure 1. Summary of the treatment for nausea and vomiting during pregnancy. 임신오조나탈수가심하게되어있는환자의경우티아민이포함된비타민제제와함께정맥수액보충이필요하며, 약물치료에도불구하고체중감소가계속되는경우비위관경장영양혹은비경구요법등을고려해야할것이다. 뿐만아니라이러한임산부에대한정서적지지도치료의중요한부분이되겠다. 임신중구역과구토에대한치료접근을요약하면다음과같다 (Fig. 1). 임신중구역과구토에대해안전하면서도효과적인데이터들은이러한환자의치료에있어많은도움이된다. 이를바탕으로담당의는모든산모에게일률적인것이아니라환자각각에게가장적합하고안전한방향으로접근해야하겠다. 중심단어 : 구역및구토, 임신 ; 임신오조 ; 치료 REFERENCES 1. Lacroix R, Eason E, Melzack R. Nausea and vomiting during pregnancy: a prospective study of its frequency, intensity, and patterns of change. Am J Obstet Gynecol 2000;182:931-937. 2. Berkovitch M, Mazzota P, Greenberg R, et al. Metoclopramide for nausea and vomiting of pregnancy: a prospective multicenter international study. Am J Perinatol 2002;19:311-316. 3. Piwko C, Ungar WJ, Einarson TR, Wolpin J, Koren G. The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program. Curr Med Res Opin 2007;23:833-840. 4. Reichmann JP, Kirkbride MS. Nausea and vomiting of pregnancy: cost effective pharmacologic treatments. Manag Care 2008;17:41-45. - 529 -
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