Hypertensive disoder during pregnancy


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미즈메디병원 최노미 선생님

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Hypertensive disoder during pregnancy

  1. 1. 2013년 6월 04일강서 미즈메디 최노미Antihypertensive Medicationsduring Pregnancy
  2. 2. ContentsI. IntroductionII. Management– Prevention– Obstetric management– Antihypertensive medicationIII. Postpartum ConsiderationIV. PrognosisV. Summary
  4. 4. Introduction -1-Hypertensive Disorders Complicating Pregnancy• Up to 10% of pregnancies• 1/3 of all maternal deaths
  5. 5. Introduction -2-Risk factors• Nulliparity• Extremes of reproductiveage 15< & >35• Black race• Hx of PET in a 1st degreefemale relative• Hx of PET in prior pregnancy• Chronic HTN• Chronic renal Disease• DM• Autoimmune diseases• Multiple Pregnancy→ twins 13 vs 6%• Hydatidiform mole• Nonimmune hydrops fetalis• Obesity → BMI<19.8 ; 4.3%BMI≥ 35; 13.3%• Smoking ; ↓ risk of HTN
  6. 6. Introduction -3-• Maternal– CVA- seizures & stroke– DIC• HELLP syndrome– End-organ failure– Placental abruption– Death• Fetus– IUGR– Oligohydramnios– Prematurity– Intra-uterine deathSevere Complications
  7. 7. Introduction -4-Definition of HTN– Elevation of BP ≥140 mmHg systolic &/or≥90 mmHg diastolic, on two occasionsat least 6 hours apart.
  8. 8. Introduction -5-Variation of BP in pregnancyNicolas Szecket, HTN in pregnancy 2004
  9. 9. Classification5 Categories of Hypertensive DisordersComplicationg pregnancy• Gestational Hypertension; 6-7% of pregnancies• Preeclampsia; 5-7%• Eclampsia; 5-7%• Superimposed Preeclampsia on ChronicHypertension; 20-25% of chronic HTN preg.• Chronic Hypertension; 1-5%
  10. 10. MANAGEMENT
  11. 11. Prevention -1-Diatery Manipulation• Low-salt diet• Calcium supplement• Fish oil supplement→ Not effectiveCardiovascular drug• Diuretics• Antihypertensive drug→ Not effective
  12. 12. Prevention -2-Low dose aspirin or LMWH with low dose aspirin Selective supression of throboxane synthesis by the plt& sparing endothelial prostacyclin production Not effective in preventing preeclampsiaBut advise women at high risk of preeclampsia totake 75mg of aspirin daily from 12wks until the birth– High Risk; HTN during a previous pregnancy, Chronic renal dz,Autoimmune dz such SLE or antiphospholipid SD, , Chronic HTN,Type 1 or type 2 DM heart (2011)Antioxidants : Vit C & E supplementation Significant reduction in preeclampsia (Poston, 2006, Villar, 2007)
  13. 13. ManagementGoals• Minimize maternal end-organ damage• Prevent seizure• Terminaton of pregnancy with the least possibletrauma to the mother & fetusSteps of management• Evaluation of HTN• Admission vs OPD f/u• No medication or medication1. Antihypertensive therapy2. Anticonvulsant therapy; MgSO4
  14. 14. ManagementHospitalization• Women with new onset BP ≥ 140/90• Worsening BP• Development of proteinuria in addition to existing BPDepends on:• Severity of HTN in pregnancy• Duration of gestation• Condition of the cervix
  15. 15. ManagementCheck up• Serial U/S for fetal growth. BPP, NST 34wk• Follow up every 2 wks till 30, then weekly• Warn the mother about symptoms of superimposed PET• Investigations ; Renal function test, uric a , calcium ,LFT,• 24hrs urine for Cr clearance & protein, CBC, U/A, ECG.GTT• Not allowed to continue past 40wks → consider induction• Regular diet no salt restriction• Indication of induction• For superimposed PET,IUGR, fetal distress, worsening renalfunction
  16. 16. ManagementIndications of Termination of Pregnancy• Term pregnancy with mild or severe PET• Severe PET regardless of the gestational age• Warning signs headache , visual disturbance, epigastric pain, oliguria• Eclampsia Pt must be stabilized & delivered immediately• Preterm with mild PET Assess fetal wellbeing by NST, BPP, Doppler
  17. 17. Drug Treatment During Pregnancy• Continuation of prepregnancy antihypertensive Txwhen women become pregnant is debatedBeneficial to mother in the long term, buttheoretically can decrease uteroplacental perfution• IUGR; from drug or effect from worsening of HTN ?• Mild to moderate HTN Tx (?)Antihypertensive Drugs -1-
  18. 18. Blood Pressure Classification; JNC-7 Compared with NHBPEPJNC-7 Blood Pressure Classification(Nonpregnant), mmHgNHBPEP Blood PressureClassification(Pregnant), mmHgNormal: SBP≤120, DBP≤80PreHTN: SBP 120-139 or DBP 80-89Stage 1 HTN: SBP 140-159 or DBP 90-99Stage 2 HTN: SBP 160-179 or DBP 100-110Stage 3 NTN: SBP 180-209 or DBP 110-119Normal/acceptable in pregnancy:SBP≤140 and DBP≤90Mild HTN: SBP 140-150 or DBP 90-109Severe HTN: SBP≥ 160 or DBP≥110JNC-7: Ther Seventh Report of the Joint National committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure.NHBPEP: National High Blood Pressure Education Program Working Group Report onHigh Blood Pressure in PregnancyAm J Obstet Gynecol. 2000Antihypertensive Drugs -2-Grade of HTN BP levels EITHERsystolic ORdiastolic (mmHg)Treat Levels after TxMild Diastolic: 90-99Systolic: 140-149No Not applicableModerate Diastolic: 100-109Systolic: 150-159Yes <150 systolic< 100 diastolicSevere HTN Diastolic: ≥ 110Systolic: ≥ 160Yes <150 systolic< 100 diastolic
  19. 19. • Randomized trials of antihypertensive drug therapy inPregnancies Complicated by Mild Chronic HypertensionPIHAntihypertensive Drugs -3-
  20. 20. • Randomized trials of antihypertensive drug therapy inPregnancies Complicated by Mild Chronic HypertensionPIHAntihypertensive Drugs -4-
  21. 21. Mild to moderate chronic or gestational HTN• Less likely to produce end-organ-disorders• So, Treatment neither improve neonatal outcomes norprevent superimposed preeclampsia• A Cochrane review of 46 trials• 4282 patients with modest BP increases• Showed no benefits of Tx in terms of stillbirth, PTL, or SGA• Excessive BP lowering in such patients-> May even prove detrimental to fetal growth via placentalhypoperfusionVon Dadelszen P, et al. J Obstet Gynaecol Can 2002;24:941–5.Antihypertensive Drugs -5-
  22. 22. Summary of Society Guidelinesregarding BP Tx thresholds & Target
  23. 23. Antihypertensive Drugs -6-• Therapy Recommendation– By the Working Group on High BP in Pregnancy(2000)– Indication for empirical therapy• BP ≥ Systolic 150~160mmHg &/or≥ Diastolic 100~110mmHgby NHBPEP & ACOG guidelines 2012• With target-organ damage(Left ventricular hypertrophy or renal insufficiency)Treatment Goal; DBP =90~100mmHg(Grade D)
  24. 24. Antihypertensive Drugs -7-• Severe or Chronic PTN in pregnancy• Used to control BP until the Pt delivers or in pretermfor 48 hrs to allow time for glucocorticoidadministration for fetal lung maturity then delivery• Drugs• Adrenergic-Blocking Agents• Diuretics• Vasodilators• CCB(Calcium channel blockers)• ACE inhibitors -CIx
  25. 25. Antihypertensive Drugs -8-Drug/Class Doses/half lifeAdverse Events in pregnancy EvidenceCommentsMethyldopa(FDA-B, L2); AdrenergicBlocking agents,centrally500mg~3gIn 2 dividedPeripheral edema, anxiety,night mares, drowsiness, drymouth, hypotension, maternalhepatitis, but no major fetaladverse eventsLarge Large postmarketingevidence onsafety1st choice drug inpreg by CardioLabetalol(FDA-C, L2); α,B-blocker200~1,200mg/d in 2-3dividedPersistent fetal bradycardia,hypotension, neonatalhypoglycemiaLarge 1st recom. ByACOG 2012Nifedipine(FDA-C, L2); CCB30mg~120mg /d of aslow-release prep.Hypotension & inhibition ofparticularly if used incombination withmagnesium sulfateSmall Immediatereleasenifedipine notrecommendHydralazine(FDA C, L2);Vasodilator50~300mg/d in 2~4dividedPotential ass. WithHypospadia, neonatalthrombocytopenia and lupusModerateEspeciallyperipartum IV
  26. 26. Antihypertensive Drugs -9-Drug/Class Doses/half lifeAdverse Events inpregnancyEvidence CommentsAtenolol(FDA-C, L2);pure b-blockerDepends onspecificagentMay decrease uteroplacentalblood flow, IUGR whenstarted 1,2nd trimester,preterm birth, bradycardianeonatal hypoglycemia,Hydrochloro-thiazide(FDA- C, L2); Diuretics12.5~25mg/dNo fetal anomaly, electrolyteabnormalities, neonatalhypoglycemia, volumedepletionLarge Not 1st line Txduring preg,esp after20wksACE inhibitor(FDA C/D in2nd & 3rd ∆,L2)Contraindicated inpregnancyOligohydramnios, IUGR,Fetal renal failure, Heartanomalies, Polydactyly,Hypospadias, SA, limb,pulmonary hypoplasia,craniofacial anomalyLarge
  27. 27. Antihypertensive Drugs -10-ACEI(Angiotnesin-Converting Enzyme Inhibitors)or angiotnesin receptor blockers ; Captopril, Lisinopril• Contraindicated during all trimesters of pregnancyMagee LA, et al. BJOG. 2007;114(6):770. e13–20.ACOG. Obstet Gynecol 2001;98(1):177–85.• Complication• Severely underdeveloped calvarial bone, renal agenesisPulmonary hypoplasia, IUGR, fetal death, neonatal renalfailure, oilgohydramnios, anuria & neonatal death,multiple cardiovascular malformationsOthers to avoid during pregnancy –FDA D category– Losartan, Valsartan, Aliskiren(direct renin inhibitor)
  28. 28. Antihypertensive Drugs -11-Summary of Antihypertensive Therapy Selection• No evidence of major adverse fetal or maternal events.• Methyldopa• 1st Choice of Tx by NHBPEP working group• No fetal anomaly in the first trimester• Vascular stiffness improved Khalil & colleagues (2009)• Labetalol• May ass with fetal growth restriction• No advantages over Methyldopa Sibai & colleagues (1990)• Nifedipine• Experiences and newer safety concerns are not sufficient topermit recommendations
  29. 29. Antihypertensive Drugs -12-Drugs for urgent control of severe acute HTN in pregnancyDrug(FDA risk) Dosage Maternal adverse effectsHydralazine (C) 5mg IV or IM, then 5-10mgevery 20-40min; orconstant infusion of 0.5-10mg/hrLong experience of safety &efficacy . Risk of delayedmaternal hypotension, fetalbradycardiaLabetalol (C) 20mg IV, then 20-80mgevery 5-15min, up to amazimum of 300mg; orconstant infusion of 1-2mg/minProbably less risk of tachycardia& arrhythmia than with othervasodilators; increasinglyperferred as 1st-line agentsNifedipine (C) 10-30mg PO, repeat in45min if neededPossible interference with laborDiazoxide (C) 30-50mg IV every 5-15 min Use is waning; may arrest labor;cause hyperglycemia
  30. 30. Fluid TherapyHyperosmotic agents not recommended becauseIntravascular influx of fluidSubsequent escape of fluid to vital organsPulmonary edema & cerebral edemaLR 60-120 ml/hr Excessive fluid administrationPulmonary edema & cerebral edema
  31. 31. Postpartum Considerations• Similar with severe chronic HTN & severe preeclampsia-eclampsia• Development of cerebral or pulmonary edema,heart failure, renal dysfunction or cerebral hemorrhage– Especially high within the 1st 48hrs after deliveryCunningham, 2005– Following delivery, as maternal pph resistance ↑,left ventricular workload ↑–> further aggrevated by appreciable amounts ofinterstitial fluid that are mobilized for extcretion asendothelial damage is repairSo Promptly HTN control with diuretic therapyfor resolving pulmonary edema
  32. 32. PrognosisMaternal death; rare– Due to cerebral Hg, aspiration pneumonia, hypoxicencephalopathy, thromboembolism, hepatic rupture,renal failure, ansthesiaRecurrence– Gestational HTN in a future pregnancy; 13~ 53%– Pre-eclampsia in a future preg; 16%– Severe preeclampsia, HELLP syndrome or eclampsiaor birth before 34wks -> Preeclampsia in a future; 25%– Birth before 28wks -> 55% heart, 2011
  33. 33. SummaryLevel A– ACE inhibitors & angiotensin receptor blockers; Contraindicated in all trimesters of pregnancyLevel B• Woman with severe HTN-> require antihypertensive medication for acute ↑BP• Methyldopa & Labetalol ; a good option for 1st line tx of chronic HTNin pregnancy -> Based on the overall low rate of adverse effects &good efficacy• Atenolol ; not currently recommended d/t IUGR• Thiazide used in women before pregnancy• No need to be discontinued during pregnancy. ACOG,2012
  34. 34. Reference1. Clinical Obstetrics and Gynecologyvol 48(2) June 2005, pp441~4592. NICE Guidelines on hypertension in PregnancySpR Training Day,21/01/20113. District I ACOG Medical Student Education Module 2011– Pregnancy induced hypertension4. Hypertension in Pregnancy.Amanda R. Vest, et al. Calrdiol Clin 30 (2012 407~423)5. Chronic Hypertension in PregnancyPractice bulletin, Vol 119, No 2, part 1, Feb 2012. ACOG
  35. 35. 경청해주셔서감사합니다.