제
34, 36 장
고혈압
서론
① 출혈 , 감염 , 고혈압은 모성사망 및 이환의 3 대 질환
② 전자간증 (preeclampsia) – 임신 중기 이후 발병하는 고
혈압 질환으로 유일하게 임신에 의하여 발병하고 임신의
종결과 함께 치유되는 내과적 합병증
③ 병태생리 및 치료법은 완전히 밝혀지지 않음 .
서론
① 임신성고혈압 (Gestational hypertension)
—
formerly termed pregnancy-induced
hypertension. If preeclampsia syndrome does not
develop and hypertension resolves by 12 weeks
postpartum, it is redesignated as transient
hypertension
② 전자간증 - 자간증 (Preeclampsia
and
eclampsia
syndrome)
③ 가중합병전자간증 (Preeclampsia syndrome
superimposed on chronic hypertension)
④ 만성고혈압 (Chronic hypertension)
Chronic hypertension 임신 전 진단되었거나 임신 20 주 전에 진단되는 고혈압 가임기 여성의 고혈압 유병률 30 대 3.4%, 40 대 10.8%(‘11) 백의고혈압 (white-coat hypertension) 고려 임신 중 혈압이 조절되는 경우가 있으며 임신경과에서 비교적 예후가 좋은 편이나 반면 , 고혈압이 악화되고 단백뇨 , 증상 및 경련이 동반되는 경우 preeclampsia 도 발생 가능 (superimposed preeclampsia)
Chronic hypertension
BP>135/85 mmHg 임신의 금기증
cerebrovascular thrombosis or hemorrhage myocardial infarction
cardiac failure
임신의 상대적 금기증
persistent diastolic pressure ≥110 mmHg multiple antihypertensives
만성고혈압 임신부의 산전관리
임신 전 또는 임신 초기에 이차성 고혈압을 감별하고 표적장기 손상
유무를 확인하기 위한 충분한 평가가 이루어져야 함 .
4-40%, superimposed preeclampsia
Uterine artery Doppler velocimetry 를 예측에 사용하기도 함 . Low dose aspirin, 예방 목적으로 투여
태아상태평가
만성고혈압 임신부의 산전관리
혈압조절
BP control, SBP>150~160 mmHg, DBP≥100 mmHg
표적장기 손상이 있으며 경증의 고혈압에서도 치료가 권고됨 .
adrenergic blocking agent (ex, methyldopa, β-blocker, αβ-blocker), CCB
ACE inhibitor, ARB 는 임신 중 사용 금기임 . 분만관련 처치
태아성장제한이나 전자간증과 같은 합병증이 발생한 경우 임상적 판
단에 의해 분만 시기를 결정함 . 분만방법 역시 산과적 요인에
Indicators of Severity of Gestational
Hypertensive Disorders
Abnormality Nonsevere Severe
Diastolic blood pressure <110 mm Hg ≥110 mm Hg Systolic blood pressure <160 mm Hg ≥160 mm Hg Proteinuria None to positive None to positive
Headache Absent Present
Visual disturbances Absent Present Upper abdominal pain Absent Present
Oliguria Absent Present
Convulsion (eclampsia) Absent Present
Serum creatinine Normal Elevated
Thrombocytopenia Absent Present
Serum transaminase elevation Minimal Marked
Fetal-growth restriction Absent Obvious
Pulmonary edema Absent Present
• The differentiation between nonsevere and severe gestational
hypertension or preeclampsia can be misleading because what might be apparently mild disease may progress rapidly to severe disease.
전자간증의 빈도 및 위험인자
Nulliparous population, 3-10%
위험인자
① Young, nulliparous women
② Obesity, multifetal gestation, >35years old women hyperhomocysteinemia, metabolic syndrome,
African-American ethnicity ※Reduced risk
원인
① Placental implantation with abnormal trophoblastic invasion of uterine vessels
② Immunological maladaptive tolerance between maternal, paternal (placental), and fetal tissues ③ Maternal maladaptation to cardiovascular or
inflammatory changes of normal pregnancy
(prostacyclin-thromboxane 의 불균형 , 산화스트레스 , 혈 관생성인자 _sFlt-1, PlGF, sEng 의 불균형 )
④ Genetic factors including inherited predisposing genes as well as epigenetic influences.
자간전증의 병인 및 기전
자간전증의 병인 및 기전
다음의 여성에서 잘 발생
->vascular endothelial damage, subsequent vasospasm, transudation of plasma, thromobotic sequelae
• Are exposed to chorionic villi for the first time
• Are exposed to a superabundance of chorionic villi, as with twins or hydatidiform mole
• Have preexisting renal or cardiovascular disease
• Are genetically predisposed to hypertension developing during pregnancy.
태반측요인
(abnormal trophoblastic
invasion)
태반측요인 (abnormal trophoblastic invasion)
• diminished perfusion, hypoxic enviroment 는 placental debris 혹은 microparticles 을 방출하여 systemic inflammatory
response 를 유발
• defective placentation 은 gestational hypertension,
preeclampsia syndrome, preterm delivery, growth-restricted fetus, placental abruption 을 유발
면역학적 요인 (immunologic factors)
Maternal immune tolerance 에 의해 정상 임신 유지
Tolerance dysregulation 에 의해 preeclampsia 발생 가능 First pregnancy
Increased paternal antigenic load (ex, molar pregnancy) Trisomy 13 (elevated antiangiogenic factor, sFLT-1)
Immune maladaptation (reduced HLA-G…)
Pathogenesis
① Vasospasm
② Endothelial cell activation
- increased pressor responses
③ Endothelin 증가
④ Angiogenic imbalance
antiangiogenic proteins 인 sFlt-1, sEng 의 증가
angiogenic protein 인 PlGF 감소
병태생리
Cardiovascular system – hyperdynamic
① 혈압상승 , 혈관수축과 비정상 혈관 반응성 (angiotensin II 에 대한
과도한 반응성 )
② 심박출량이 보통이거나 약간 감소
병태생리
Blood volume-Severe hemoconcentration
It is important to recognize that a substantive cause of this fall in hematocrit is usually the consequence of blood loss at delivery.
병태생리
혈액 및 응고인자 변화
• Thrombocytopenia
• Hemolysis
• HELLP syndrome (hemolysis, low platelet, elevated liver enzyme)
• Coagulation – subtle changes like intravascular coagulation
병태생리
Volume homeostasis Endocrine changes:
• renin, angiotensin II, angiotensin 1-7, aldosterone 의
감소 ( 정상임신에서는 증가 )
• Deoxycorticosterone 증가
• Vasopressin, atrial natriuretic peptide 는 비슷함 . Fluid and electrolyte changes:
• Extracellular fluid 의 증가에 의한 edema (endothelial injury 에 의해 발생 )
병태생리
Kidney
Anatomical changes-glomerular endotheliosis 사구체여과율과 신장혈류량의 감소 Proteinuria (>300mg/24h), 단백뇨량으로 질병의 중증도를 평 가하지 않음 . Prerenal oliguria 가 나타남 Cr 이 1 mg/mL 이상 상승하나 분만 후 10 일내에 정상화됨 . Oliguria 는 수액정주가 치료법은 아님 .
병태생리
Liver
HELLP syndrome – hemolysis, hepatocellular necrosis, thrombocytopenia
간효소수치의 현저한 증가 (elevated AST and ALT)
피막혈종 혹은 간파열이 발생할 수 있음 (Hepatic hemorrhage, subcapsular hematoma, rupture)
임상증상 - 우상복부통증 (epigastric pain)
※ Acute fatty liver of pregnancy is sometimes confused with preeclampsia
병태생리
Brain 임상증상
① Headache and scotomata blurred vision, diplopia
② Convulsion – eclampsia magnesium sulfate 투여
③ Blindness, 대부분 resolution 되며 무증상의 serous retinal detachment 는 흔한 편임 .
④ Generalized cerebral edema – mental change, 갑작스
병태생리
Brain (headache)
•
cerebral hemorrhage
•
seizure
예측
(predictive tests for development of the
preeclampsia)
Testing Related To: Examples Placental perfusion/vascular resistanceRoll-over test, isometric handgrip or cold pressor test,
angiotensin-II infusion, midtrimester mean arterial pressure, platelet angiotensin-II binding, renin, 24-hour ambulatory
blood pressure monitoring, uterine artery or fetal transcranial Doppler velocimetry
Fetal-placental unit endocrine
dysfunction
Human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), estriol, pregnancy-associated protein A (PAPP A), inhibin A, activin A, placental protein 13, corticotropin-releasing
hormone, A disintegrin, ADAM-12, kisseptin
Renal dysfunction Serum uric acid, microalbuminuria, urinary calcium or kallikrein, microtransferrinuria, N-acetyl-β-glucosaminidase, cystatin C, podocyturia
Endothelial
dysfunction/oxidant stress
Platelet count and activation, fibronectin, endothelial adhesion molecules, prostaglandin, thromboxane, C-reactive protein, cytokines, endothelin, neurokinin B, homocysteine, lipids, antiphospholipid antibodies, plasminogen activator-inhibitor (PAI), leptin, p-selectin, angiogenic factors to include placental growth factor (PlGF), vascular endothelial growth factor
(VEGF), fms-like tyrosine kinase receptor-1 (sFlt-1), endoglin Others/miscellaneo
us Antithrombin-III(AT-3), atrial natriuretic peptide (ANP), βmicroglobulin, haptoglobulin, transferrin, ferritin, 25- 2
-hydroxyvitamin D, genetic markers, cell-free fetal DNA, serum and urine proteonomics and metabolomic markers, hepatic aminotransferases
예방 (some methods to prevent preeclampsia that have been evaluated in randomized trials)
위의 어느 것도 예방효과가 확립된 것은 없음 .
Preeclampsia 발생 고위험에서 low dose aspirin 은 예방 목적으로 권장 .
Dietary manipulation—low-salt diet, calcium supplementation,
fish oil supplementation
Exercise – physical activity, stretching
Cardiovascular drugs—diuretics, antihypertensive drugs
Antioxidants—ascorbic acid (vitamin C), α-tocopherol (vitamin
E), vitamin D
Antithrombotic drugs—low-dose aspirin, aspirin/dipyridamole,
치료
Preeclampsia 발생이 의심되면 (suspected) 자주 산전진찰을 받도 록 하여야 함 .
조기 발견
① Termination of pregnancy with the least possible trauma to mother and fetus
② Birth of an infant who subsequently thrives ③ Complete restoration of health to the mother
One of the most important clinical questions for
successful management is precise knowledge of fetal
age.
평가 (Early diagnosis of preeclampsia) - hospitalization
① Detailed examination followed by daily scrutiny for clinical findings such as headache, visual disturbances, epigastric pain, and rapid weight gain
② Weight determined daily
③ Analysis for proteinuria on admittance and at least every 2 days thereafter
④ Blood pressure readings in the sitting position with an
appropriate-size cuff every 4 hours, except between 2400 and 0600 unless previous readings had become elevated ⑤ Measurements of plasma or serum creatinine and liver
transaminase levels, and hemogram to include platelet
quantification. The frequency of testing is determined by the severity of hypertension. Some recommend measurement of serum uric acid and LDH levels and coagulation studies. However, the value of these tests has been called into
question.
⑥ Evaluation of fetal size and well-being and amnionic fluid volume, with either physical examination or sonography.
치료 , Consideration for delivery
Termination of pregnancy is the only cure for preeclampsia. • severity of preeclampsia
• gestational age
• condition of the cervix
Severe preeclampsia demands anticonvulsant and usually antihypertensive therapy followed by delivery.
Preterm 으로 임신을 유지하고자 할 때 fetal well-being test (NST or BPP) 를 반드시 평가하여야 함 .
Labor induction or cesarean delivery
질식분만을 위한 유도분만 가능하나 성공적인 유도분만을 방해하는 소
치료
Mild and moderate hypertension
1) hospitalization vs outpatient management 2) antihypertensive therapy
3) 37 주 이후 면 분만을 고려하나 38 주 이전에 신생아 이환율이 증
치료
중증 전자간증 - 자간증에 준해서 치료 ( 항경련제 , 항고혈압제 + 분만 )
34 주 이후 중증의 고혈압이 발생하거나 34 주 전이라도 산모나 태아에게 위
험한 상황이라면 분만
Early-onset severe preeclampsia (24~34 주 전의 전자간증 ) 1) delayed delivery, to improve neonatal outcome
; controversies
; few beneficial effect
; serious maternal complication (placental abruption,
pulmonary edema, eclampsia, cerebrovascular hemorrhage, maternal death)
2) Glucocorticoids for lung maturation
3) Corticosteroids to ameliorate HELLP syndrome ; no advantages
자간증 (Eclampsia) – generalized tonic-clonic convulsion 대부분의 경련은 분만 중 혹은 분만 후에 발생
placental abruption, neurological deficits, cerebral hemorrhage, aspiration pneumonia, pulmonary edema, HELLP syndrome, cardiopulmonary arrest, acute renal failure, death
자간증의 치료
① Control of convulsions using loading dose of
magnesium sulfate.
② Intermittent administration of an antihypertensive medication to lower blood pressure whenever it is considered dangerously high
③ Avoidance of diuretics unless there is obvious
pulmonary edema, limitation of intravenous fluid administration unless fluid loss is excessive, and avoidance of hyperosmotic agents
④ Delivery of the fetus to achieve a remission of preeclampsia
Magnesium sulfate to control convulsions 자간증 , 중증 전자간증
경증의 전자간증 임신부에게 황산마그네슘의 예방적 치료에 대해서는 논란이 있음 .
진통 동안과 분만 후 24 시간 동안 사용 is not given to treat hypertension
for eclampsia, continued for 24 hours after the onset of convulsion
마그네슘황산염의 약리학 , 독물학
therapeutic range, 4.8~8.4 mg/dL, 4~7 meq/L GFR 을 확인하기 위해 혈중 크레아티닌 수치를 확인
GFR 이 감소되어 Cr>1.0 이면 유지 용량을 줄이는 것이 권장 . 독성 ; ~ 10meq/L (12 mg/dL), patellar reflex disappear > 12meq/L, respiratory paralysis and arrest
• calcium gluconate or calcium chloride, 1 g intravenously, along with withholding further
magnesium sulfate, usually reverses mild to moderate respiratory depression.
마그네슘황산염 투약시 확인사항
• the patellar reflex is present • Respirations are not depressed
• Urine output the previous 4 hrs exceeded 100mL 자궁에 대한 효과 초기 부하량을 정주하는 동안 일시적인 자궁수축의 감소가 있지만 지속적인 영향을 미치지는 않음 . 옥시토신 자극 , 분만까지의 시 간 , 분만방법에 차이가 없음 . 태아에 대한 영향 일시적으로 태아심박동의 변이가 감소될 수 있으나 이로 인해 나쁜 결과가 초래되지는 않음 . neuroprotection for VLBW
Who should be given magnesium sulfate?
Severe preeclampsia & eclampsia should be given magnesium sulfate prophylaxis.
항고혈압 약제 치료
Management of severe hypertension
SBP ≥ 160mmHg or DBP ≥110mmHg ① Hydralazine 5mg (IV) q 15-20min ② Labetolol 10~20mg (IV) q 10min ③ Nifedipine 10mg (PO) q 30min
④ Diuretics-not used to lower blood pressure to treatment of pulmonary edema
자간증의 분만
Cesarean delivery
Vaginal delivery, labor induction, often labor spontaneously These women, who consequently lack normal pregnancy
hypervolemia, are much less tolerant of even normal blood loss than are normotensive pregnant women.
Counseling for future pregnancies
Long-term sequences
Cardiovascular and neurovascular morbidity hypertension
ischemic heart disease stroke
Renal sequelae
chronic renal disease Neurological sequelae