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1 Anesth Pain Med 2013; 8: 종설 산후출혈의진단과관리 경희대학교의과대학마취통증의학교실 박성욱 Diagnosis and management of postpartum hemorrhage Sung Wook Park Department of Anesthesiology and Pain Medicine, College of Medicine, Kyung Hee University, Seoul, Korea Postpartum hemorrhage (PPH) is an important cause of maternal mortality. There is currently no single, satisfactory definition of PPH. The various definitions of PPH may result in delayed diagnosis. Underestimated blood loss concerning PPH is considered one of the biggest problems. The diagnosis of PPH should include proper estimation of blood loss before vital signs and clinical symptoms change. Management of PPH involves early recognition, assessment and resuscitation. Careful monitoring of vital signs, laboratory tests, coagulation testing in particular, and timely diagnosis of the cause of PPH are important. The first priority in the management of PPH is the rapid correction of hypovolemia with fluid infusion and packed red blood cells transfusion, followed by blood component therapy as indicated by the hematocrit, coagulation tests, platelet count and clinical features. Pharmacological management of PPH is to contract uterus (e.g., oxytocin, methylergonovine, 15-methylprostaglandin F2α, misoprostol) and to aid hemostasis (e.g., tranexamic acid, recombinant factor VIIa). Surgical management (e.g., balloon tamponade, uterine compression suture, iliac artery ligation) should be considered if hemorrhage persists or vital signs is unstable. (Anesth Pain Med 2013; 8: ) Key Words: Blood transfusion, Postpartum hemorrhage, Uterotonics. 산과적출혈은모성사망의약 25% 에해당하는원인이며, 분만 3기합병증인분만후첫 24시간안에발생하는산후 Received: July 9, Revised: July 12, Accepted: July 15, Corresponding author: Sung Wook Park, M.D., Department of Anesthesiology and Pain Medicine, College of Medicine, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul , Korea. Tel: , Fax: , 출혈 (postpartum hemorrhage) 로인한사망이산후사망의약 50% 의원인에해당한다 [1]. 산후출혈은선진국에서의 3대모성사망의원인인색전증, 고혈압다음으로빈도가높은것으로알려져있으며 [2], 미국에서는주산기중환자실입실과모성사망의가장많은원인으로알려져있다 [3]. 산후출혈이발생한이후즉각적인인지와함께적절하게처치하는것이중요한데, 출혈의진단과치료가지연되거나적절한처치에도불구하고짧은시간동안다량의출혈로인해저혈량성쇼크와파종성혈관내응고, 신부전, 간부전, 급성호흡기곤란증등을유발하여모성이환율과사망률을증가시키기때문이다 [4]. 이종설에서는산후출혈의정의와진단, 위험인자에대해알아보고이를통한산모의적절한관리에대해살펴보고자한다. 산후출혈의정의및진단일반적으로산후출혈은출혈의발생시기에따라분류하게되는데분만후 24시간이내에발생하는일차성산후출혈과분만 24시간후부터 12주미만에발생하는이차성산후출혈로분류한다. 산후출혈의전통적인정의는질식분만후산도를통한실혈량이 500 ml 이상인경우이며치료하지않는다면출혈성쇼크와사망에까지이르게할수도있다 [5]. 또한제왕절개시의경우에는실혈량이 1,000 ml 이상의경우를산후출혈이라고정의한다 [6]. 그러나방사성동위원소희석법 (radioisotope dilution techniques) 을이용하여측정한제왕절개시실혈량은 1,290 ± 240 ml로서산부인과의사들이기록한추정실혈량보다상당히많은데이는실혈량이실제보다저평가되고있다는것을의미하며 [7], 임상적인측정을통한질식분만과제왕절개의평균실혈량은각각 500 ml, 1,000 ml 이상이라고알려져있다 [8]. 또한심한산후출혈은일반적으로 1,500 ml 이상의출혈로정의되는데 [9] 현재출혈량에따른산후출혈의정의는다양해서 ACOG (The American College of Obstetricians and Gynecologists) 에서는단독정의로만족할만한것은없다고하였다 [10]. 임상증상과징후의고려없이출혈량만으로산후출혈을정의하는것은환자관리의문제점이발생할수있다. 건강한여 209

2 210 Anesth Pain Med Vol. 8, No. 4, 2013 성에서는 1,000 ml 정도의급성출혈에도혈역학적변화없이견딜수있으나심한빈혈여성에서는 250 ml 정도의출혈에도임상적으로좋지않은결과를나타낼수있다 [11]. 적혈구용적율의변화에따른산후출혈의정의는비교적객관적이며상대적으로정확한데다일반적으로산전산후검사시적혈구용적율을검사하기때문에쉽게판단할수있는장점이있다 [12]. 분만시의출혈뿐만아니라분만후지연된출혈에의해서도적혈구용적율수치가변화하므로이러한수치변화를통해수혈여부를결정하는것은임상적으로적절할것이다 [13]. 하지만적혈구용적율변화에따른산후출혈의정의는응급상황을초래할정도의급성출혈에서는출혈의정도가적혈구용적율이나혈색소에반영되지못하므로임상적인유용성이떨어질수있다. 따라서산후적혈구용적율이나혈색소의감소와같은검사결과의변화를통해산모의위험을초래할정도의응급상황여부를판단하는것은적절하지않다. 심한산후출혈은추정실혈량과실혈속도, 주산기혈색소의감소정도, 농축적혈구수혈량에의해정의되지만 [4] Rajan과 Wing은 [14] 이러한수치적결과에따른판단이아니라과도한출혈에따른증상과징후를통한산후출혈의정의를주장하였다. 일반적으로출혈량이 1,000 ml 이상일경우빈맥이발생하게되지만혈압은유지된다. 1,500 ml 정도의출혈이있을경우임상징후가나타나게되는데맥박과호흡수가증가하고 1,500 ml 이상의출혈이발생하게되면수축기혈압이 80 mmhg 이하로감소하고빈맥과빈호흡이악화되며환자의의식상태도저하된다 (Table 1) [4]. 그러나임신기간중순환혈액량의증가로인해저혈량쇼크로인한활력징후의변화는인지하기어려울수도있다. 출혈량이많아보상기전으로도활력징후가유지되지않는경우에이러한증상과징후가나타나게되므로이는증상과징후를통한산후출혈의정의의문제점이라할수있다. 또한임신으로인해저혈량증을조기에인지하기힘들게되고그로인해치료가지연될수있는데이러한지연으로인해추가적인출혈이발생하여출혈성쇼크의위험이더욱증가하게된다 [15]. 산후출혈진단을위한원칙으로는먼저분만전산후출혈의위험성이높은산모인지조기에확인하는것이중요하다. 또한활력징후의변화가있기전실혈량을제대로측 정할수있어야한다. Bose 등은 [15] 육안으로실혈량을추정하는것은교육과훈련을통해많이향상될수있다고하였다. 광도측정법 (photometric technique) 을통한실혈량의측정은정확하므로실험연구에서는유용하지만임상에서의사용에는적합하지않다 [8]. 산후출혈로추정되는산모는주의깊게관찰하여혈역학적으로불안정해지기전에산후출혈의발생을인지하는것이중요하며응고장애가발생하는지확인하기위해혈액응고검사를시행해야한다. 분만후활력징후의변화를보인다면이미과도한출혈이있었음을의미하므로분만후활력징후의주의깊게감시해야하고, 출혈량의정도를객관화하여측정하는것이중요하다. 이를위해그림을이용한알고리듬과 [15] modified early obstetric warning system (MEOWS) [16] 등이도움이된다. 환자의의식상태, 맥박, 혈압, 호흡수, 체온을측정하여점수화한 MEOWS는환자의이환을예견하는데유용한도구이다. 비정상적인 MEOWS 점수를계산하여초기의출혈징후를예견할수있으며이를적절하게사용한다면조기에산후출혈이심해지는것을예방할수있을것으로보고하고있다 [16]. 이러한관찰을통해산후출혈의원인을조기에진단하여즉각적인치료를시작해야한다. 산후출혈산모관리의문제점으로는다양한산후출혈의정의로인해진단이지연될수있으며의료진구성원간의원활하지못한의사소통, 측정이부정확하고저평가된분만시출혈량등의원인으로인해적절한치료가이루어지지않을수있다는점이다 [17]. 또한적절한치료가이뤄지더라도질식분만의 3% 와제왕절개분만의 6 8% 는분만후심한산후출혈로진행할수있다 [12,18]. 산후출혈의원인과위험인자임신중심박출량은증가하게되는데태아만출기에는산통전에비해심박출량이 45% 더증가하고분만직후에는산통전에비해 80% 가더증가한다. 분만후자궁이수축하게되면대동맥압박이커져자궁동맥으로가는혈액량이줄고동시에자궁내압이상승하여자궁내혈액이융모사이공간밖으로밀려나서난소동맥을통해중심순환으로돌아가게된다 [19]. 분만후자궁출혈은자궁근의수축을통한태반으로공급되는혈관의수축, type-1 plasminogen acti- Table 1. Hemorrhagic Shock and Blood Loss in Pregnancy Blood volume loss Blood pressure Symptoms and signs Degree of shock 10 15% (500 1,000 ml) 15 25% (1,000 1,500 ml) 25 35% (1,500 2,000 ml) 35 45% (2,000 3,000 ml) Normal Slight fall mmhg mmhg Palpitations, dizziness, tachycardia Weakness, sweating, tachycardia Restless, pallor, oliguria Collapse, air hunger, anuria Compensated Mild Moderate Severe

3 박성욱 :Postpartum hemorrhage 211 vator inhibitor 등과같은탈락막의국소적지혈인자와전신응고인자에의해조절되는데이와같은출혈조절에문제가생겼을때산후출혈의원인이된다. 즉자궁근육무력증 (uterine atony) 과같이자궁근육의수축이부족한경우나유착태반 (placenta accreta) 과같이탈락막에서의지혈에문제가있는경우, 혈소판감소증이나응고인자결핍과같은출혈경향이있는경우가이에해당한다. 자궁근육무력증은산후출혈의가장흔한원인으로 20건의분만당 1건의발생빈도를가지며, 산후출혈의약 80% 의원인에해당한다 [2]. 다태임신, 양수과다증등으로인해자궁이과도하게팽창하는경우와자궁감염, 자궁이완제의사용, 유도분만, 자궁내번증 (uterine inversion), 잔류태반 (retained placenta) 등이자궁근육무력증의위험인자로알려져있지만이러한위험인자가없어도자궁근육무력증은발생할수있다 [12]. 분만후자궁의수축력이충분하다고판단되면다른출혈의원인을고려해야하지만자궁이국소적으로수축이되지않는경우신체검사로는확인이어려울수있으므로주의가필요하다. 산도의손상으로인한출혈은주로겸자분만과같이기구를사용한분만에서주로발생하며산도의열상이발생한경우와외음부절개술과같이절개를시행하는경우, 자궁파열등에의해산후출혈이발생할수있다. 임신중대부분의혈액응고인자가증가되어있으며, 혈소판은생산과소모가증가하고기능은항진되어있다. 혈소판수는임신 3기에약간감소할수있으며분만후증가하는데 8% 의산모에서혈소판감소가나타날수있다 [19]. 대개경미한혈소판감소증은다른부작용과관련이없으나지혈장애와더불어출혈경향을보일수도있다. 간에서응고인자의합성이잘안되는경우, 혈액희석, 파종성혈관내응고등에의한유발된응고장애가산후출혈을일으키게된다. 산후출혈을유발하는응고장애를일으키는원인으로는심한전자간증, HELLP 증후군, 태반조기박리 (placenta abruption), 태아사망, 양수색전증, 패혈증등이있다. 산후출혈은몇가지알려진위험인자가있지만예방하거나예측하기어려운경우가많다 (Table 2) [10,20-22]. Sheiner Table 2. Factors Associated with Postpartum Hemorrhage Retained placenta Failure to progress, 2nd stage Placenta accreta Lacerations Instrumental deliveries Large for gestational age Hypertensive disorders Induction of labor Oxytocin augmentation 등은 [21] 154,311건의분만중에서산후출혈이발생한 666건을대상으로위험인자에대한비교연구를한결과위험인자중에서잔류태반이산후출혈과연관성이가장높으며 (OR 3.5, 95% CI ), 분만 2기에서진행이되지않는경우 (OR 3.4, 95% CI ), 유착태반 (OR 3.3, 95% CI ), 열상 (OR 2.4, 95% CI ), 겸자분만 (OR 2.3, 95%CI ), 임신나이보다큰신생아 (OR 1.9, 95% CI ), 고혈압 (OR 1.7, 95% CI ), 유도분만 (OR 1.4, 95% CI ), oxytocin을이용한분만촉진 (OR 1.4, 95% CI ) 의순서로산후출혈과연관성이있다고하였다. 이외에도전치태반 (placenta previa), 산후출혈의과거력, 비만, 경산, 급속분만 (precipitate labor), 분만 1기가 24시간이상지속되는경우, 자궁의과잉팽창, 감염, 전자간증등이위험인자로알려져있다 [12,23,24]. 산후출혈의관리산후출혈관리의목표는순환혈액량을적절히유지하여주요장기로의관류저하가발생하지않도록하고신체조직의산소화가적절히유지되도록한다. 또한응고병증이발생하지않도록하며산후출혈의원인을해결하는것이다 [25]. 태아만출후에는분만 3기의적극적인관리가중요하다. 분만시예방적 oxytocin 투여와 15초이상자궁기저부마사지, 태반만출시조심스러운제대견인등과같은분만 3 기의적극적인관리를통해산후자궁무력증의위험성을감소시킬수있다 [26]. 산후출혈이발생하면먼저교질용액이나정질용액과같은수액을투여하기위해 2개의큰구경 (18G 또는 16G) 의혈관접근이필요하다. 그리고충분한산소의공급이중요한데환자의의식이있을경우안면마스크를통해 O L/min를투여하고, 의식이없는경우기관내삽관을통해 100% O 2 를투여한다 [27]. 또한출혈의원인파악을위한진단적검사를시행해야하며자궁무력증, 산도의손상, 잔류태반, 응고장애와같이흔한원인에대해서우선적으로확인이필요하다. 산후출혈발생시즉각적으로수액의투여가시작되어야하며동시에활력징후와소변량을확인해야한다. 수액을투여하는목표는수축기혈압이 90 mmhg, 시간당소변량이 30 ml 이상이되도록투여한다 [28]. 정질용액을투여하는경우예상실혈량의 3 4배의수액을투여하여야하며다량의수액이투여되는경우응고장애를유발할수있는저체온증에빠지지않도록주의를기울여야한다. 정질용액 2,000 3,000 ml를투여하였음에도산모의혈역학적소견이개선되지않고출혈이지속되는양상을보이면수혈을고려해야한다. 대량출혈이발생한경우혈액성분의수혈요법이수액의

4 212 Anesth Pain Med Vol. 8, No. 4, 2013 Table 3. Recommended Uses and Effects of Blood Products Product Contents Uses and effects Whole blood (1 unit = 500 ml) Red cells + additive solution (1 unit = 350 ml) Frozen plasma (1 unit = ml) Cryoprecipitate (1 unit = ml) Whole blood-derived and apheresis-derived platelets (1 unit = ml) All components Red cells All clotting factors, but no platelets Fibrinogen, factors VIII, XIII, VWF Platelets Rarely required. Consider when massive bleeding requires transfusion of >5 to 7 units of packed red cells. One unit increases hematocrit by 3 percentage points and hemoglobin by 1 g/dl. Best used to correct deficiencies of multiple coagulation factors (eg, DIC, liver disease, warfarin overdosage). One unit FFP increases fibrinogen by 7 to 10 mg/dl. Usual dose is 10 to 15 ml/kg. Typical dose consists of two bags of prepooled cryoprecipitate (total of 10 units), which will raise plasma fibrinogen by 70 mg/dl in a 70 kg recipient. Six units of whole blood-derived or one unit of apheresis-derived platelets will raise the platelet count by approximately 30,000/μl in an average sized adult. 투여보다중요한데 [29], 아직까지혈액성분수혈요법의기준에대해서일치된의견은없으며 [30], 투여에따른효과는 Table 3과같다. 희석성응고장애의발생을막기위해농축적혈구투여와함께혈장성분을투여해야하며 [31], 그러기위해농축적혈구와신선냉동혈장, 혈소판을적절한비율로투여해야하는데그비율에대해서는다양한의견들이있다 [30,32]. 검사결과상응고에문제가없다면농축적혈구 1 2 unit당신선동결혈장 1 unit을투여하는데 [29], Borgman 등은 [33] 24시간동안 6 unit 이상의농축적혈구를수혈했던사고환자에서조기에수혈을시작하고농축적혈구와신선냉동혈장, 혈소판을 1 : 1 : 1의비율로수혈했을때개선된결과를보였다고하였다. 수혈하는동안검사를통해혈색소가 g/dl이될때까지수혈을지속해야하며 [34], PT와 PTT는정상치의 1.5 배미만, 혈소판은 50,000 70,000/μl 이상, 섬유소원은 2 g/l 이상을목표로성분수혈을한다 [35]. 혈색소수치가낮으면혈류가빨라져혈소판응집이잘이뤄지지않고심허혈도초래될수있으므로혈색소 8 g/dl를권장한다 [36]. Oxytocin은산후출혈의예방과치료에있어가장선호되는 1차약제로서분만 3기의출혈을감소시키며추가적인자궁수축제의필요성을감소시킨다 [26]. Oxytocin 3 IU의투여로재왕절개분만산모의 90% 에서수축력이유지될수있다 [37]. 그러나 oxytocin을빠르게정맥투여하게되면말초혈관확장, 저혈압, 심근경색, 심혈관계허탈등의부작용이발생할수있는데 [38], 이와같은경우 phenylephrine 투여를통해치료할수있다 [39]. 시간당 IU의 oxytocin 이투여되고있는경우에는 oxytocin을증량하는것보다다른약제를추가하는것이더욱효과적인데이러한자궁수 축제로서 methylergonovine, carboprost tromethamine (15-Methylprostaglandin F 2α), misoprostol 등을투여할수있다 (Table 4) [20]. Carbetocin은 oxytocin의유사체로서작용시간이더욱길고, 100 μg을정주또는근주로투여한다. 약제의역가와부작용은 oxytocin과유사하다 [40]. Methylergonovine는 ergot alkaloid계열의약제로투여시빠르게자궁을수축시켜자궁무력증의치료에효과적이다. 투여시심한혈관수축을일으킬수있으며이로인해심한고혈압, 폐부종, 허혈성심질환등을초래할수있기때문에전자간증, 심혈관질환, 고혈압등을가진산모에서는투여를권장하지않고정맥으로일시에투여하지않는다 [20]. Carboprost tromethamine 은 prostaglandin계열의약제로자궁근육세포내로칼슘농도를증가시켜자궁근육의수축을증진시키게되므로산후출혈에유용하게사용될수있다. 그러나투여시기관지수축을유발할수있어천식의병력이있는산모에서는투여에주의를기울여야한다. Misoprostol은합성 prostaglandin E1 유사체로서경구, 설하, 직장내투여시잘흡수되므로주사투여가불가능한상황에서출혈을감소시키는데매우유용하다 [41]. Misoprostol의적정용량과투여경로는아직확실하지않지만, 설하로투여하는경우발현시간이빠르고지속시간도충분하여좋은투여경로로보이며 [42], World Health Organization (WHO) 에서도 misoprostol 800 μg을설하로투여하는것을권장하고있다 [43]. 하지만 Widmer 등은 [41] 1,422명의산후출혈환자를대상으로 oxytocin 10 IU 주사와 misoprostol 600 μg를설하로투여한군과 oxytocin 10 IU 주사와위약을투여한군을비교하였는데, 출혈에대해두군간의의미있는차이가없었다고보고하였다. Misoprostol은고혈압이나천식이있는산모에서도사용이

5 박성욱 :Postpartum hemorrhage 213 Table 4. Uterotonic Agents for Postpartum Hemorrhage Drug Dose and route Contraindications Side effects Notes Oxytocin Methylergonovine (methergine) 15-methylprostaglandin F 2α (carboprost) Misoprostol (cytotec) U/L IV infusion 0.2 mg IM 250 mg IM or IU 800 1,000 μg per rectum None Hypertension Preeclampsia Coronary artery disease Reactive airway disease Pulmonary hypertension Hypoxemic patients None Decreased systemic vascular resistance and hypotension with bolus IV doses Free water retention Thromboembolic sequelae? Severe nausea and vomiting Arteriolar constriction Bronchoconstriction Shivering Temperature elevation Diarrhea Shivering Temperature elevation Diarrhea Nausea/vomiting Short duration of effect May be repeated once after 1 hr May be repeated every 15 min up to 2 mg Off-label use 가능하지만투여한산모에서오한과고열이발생할수있으므로주의깊은관찰이필요하고이러한부작용은고용량을사용했을경우에더흔하게나타난다 [44]. 자궁수축제를충분히사용했음에도불구하고출혈이지속되는산후출혈에서는 tranexamic acid을투여할수있다. 지혈과정에서손상된혈관에서빠르게섬유소망이형성되어응고가이루어지고동시에섬유소침착물의용해가일어나손상된혈관이완전히막히지않게한다 [45]. Tranexamic acid는강력한항섬유소용해성약제로서 plasminogen 분자의 lysine 부착부위를차단하는작용을나타내며이를통해환자의지혈작용을강화시키고섬유소용해를방해하여출혈을감소시킨다 [45,46]. Sekhavat 등은 [47] 예정된제왕절개수술에서수술전 tranexamic acid를투여하였을때산후 2시간이내출혈이감소하였고산후 24시간후의혈색소수치가높았으며부작용이나합병증또한발생하지않았다고하여산후출혈에대한예방적인효과가있음을보여주었다. 활성유전자재조합응고인자 VII (Recombinant factor VIIa) 은응고장애로초래된출혈의예방과치료에사용되며, 가격이매우비싸사용에어려움이있다. Alfirevic 등은 [48] 등록연구를통해다른중재가실패한경우에활성유전자재조합응고인자 VII을투여하였을때출혈조절의성공률이 80% 라고보고하였다. 투여하는경우저체온증, 산혈증, 저칼슘혈증등과같은응고를저해하는요인이없는지확인하는것이중요하다. 일반적인내과적치료에호전되지않는산후출혈의경우수술적치료를고려해야한다. 산도의손상이나잔류태반이원인인경우에는즉각적으로수술적치료를시행할필요가있으나자궁무력증이나응고이상과같은원인의경우 에는수술적치료를시행할시점에대해아직확실하게알려지지않았다 [35]. 보존적치료로는풍선압박술, 자궁압박봉합술, 장골동맥결찰술등이있는데각각의방법에대해치료성공률의유의한차이가없으므로분만방법이나출혈부위에따라치료방법을결정한다 [49]. 산모의활력징후가안정적이라면차후가임을위해보존적인치료를우선해야하지만심혈관계허탈을나타낼정도의다량의출혈이발생한경우에는응급개복술은물론자궁절제술과같은근치적처치가필요할수있다 [50]. 결론적으로산후출혈은단시간에다량의출혈이발생하여적절히치료하지않을경우치명적인결과를초래할수있기때문에조기에진단하는것이성공적인산후출혈의관리를위해서중요하다. 따라서활력징후의주기적감시와혈색소나적혈구용적률과같은혈액검사, 출혈량이증가로인한임상증상등을종합적으로판단하여활력징후가불안정해지기전에수액의투여, 성분수혈, 자궁수축제의투여등의적절한관리를시작하여산후출혈을조절해야한다. 이와같이산후출혈에대한이해와지식을바탕으로조기에진단하고적절한처치를통해산모의안전을도모하고나아가모성사망률을감소시킬수있을것이다. 참고문헌 1. Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006; 367: Dildy GA 3rd. Postpartum hemorrhage: new management options. Clin Obstet Gynecol 2002; 45: Berg CJ, Callaghan WM, Syverson C, Henderson Z. Pregnancyrelated mortality in the United States, 1998 to Obstet

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노영남

노영남 Purpose: Delayed massive hemorrhages from pseudoaneurysm rupture of the peripancreatic large arteries, after pancreaticoduodenectomy, are fatal. We reviewed the clinical course and outcome of bleeding