Hypertensive Disorder in Pregnancy Untuk Kuliah

8/3/2019 Hypertensive Disorder in Pregnancy Untuk Kuliah

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Hypertensive Disorders inHypertensive Disorders in

PregnancyPregnancy



ScopeScope

Terminology and classificationTerminology and classification

Risk factorsRisk factors

EtiologyEtiology PathophysiologyPathophysiology

Prediction and preventionPrediction and prevention

ManagementManagement



IncidenceIncidence

33..77 % of pregnancies% of pregnancies

1616% of pregnancy% of pregnancy--related deathsrelated deaths

EclampsiaEclampsia 11 inin 20002000 deliveriesdeliveries



ClassificationClassification

by the working group of theby the working group of theNHBPEP (NHBPEP (20002000))

11. Gestational hypertension. Gestational hypertension

22. Chronic hypertension. Chronic hypertension

33. Preeclampsia. Preeclampsia

44. Eclampsia. Eclampsia55. Preeclampsia superimposed on chronic. Preeclampsia superimposed on chronic

hypertension (superimposed preeclampsia)hypertension (superimposed preeclampsia)



I. Gestational hypertensionI. Gestational hypertension

BP >=BP >= 140140//9090 mmHg for first time duringmmHg for first time during

pregnancypregnancy

No proteinuriaNo proteinuria BP returns to normal <BP returns to normal < 1212 wk postpartumwk postpartum

Final diagnosis made only postpartumFinal diagnosis made only postpartum

May have other signs & symptoms of May have other signs & symptoms of preeclampsia , eg. epigastric discomfort or preeclampsia , eg. epigastric discomfort or thrombocytopeniathrombocytopenia



II. Chronic hypertensionII. Chronic hypertension

BP >=BP >= 140140//9090 mmHg before pregnancy or mmHg before pregnancy or

diagnosed beforediagnosed before 2020 wk , not attributablewk , not attributable

to GTD or to GTD or Hypertension first diagnosed after Hypertension first diagnosed after 2020 wkwk

and persistent after and persistent after 1212 wk postpartumwk postpartum



Underlying causes of Underlying causes of Chronic HypertensionChronic Hypertension

Essential familial hypertensionEssential familial hypertension

ObesityObesity

Arterial abnormalities Arterial abnormalities

Endocrine disordersEndocrine disorders

GlomerulonephritisGlomerulonephritis

Renoprival hypertensionRenoprival hypertension

Connective tissue disease

Connective tissue disease

PCKDPCKD

ARF ARF



III. PreeclampsiaIII. Preeclampsia



PreeclampsiaPreeclampsia

Mild preeclampsiaMild preeclampsia

BP >=BP >= 140140//9090 mmHg after mmHg after 2020 wk gestationwk gestation

Proteinuria >=Proteinuria >= 300300 mg/mg/2424hr or >=hr or >=11+ dipstick+ dipstick



Severe preeclampsiaSevere preeclampsia

Anyone who meets at least two of the Anyone who meets at least two of thefollowing signs:following signs:

BP >=BP >= 160160//110110 mmHgmmHg

ProteinuriaProteinuria 55 g/g/2424hr or >=hr or >= 22+ dipstick (persistent)+ dipstick (persistent)

Cr >Cr > 11..22 mg/dlmg/dl

Platelets <Platelets < 100100,,000000 /mm/mm33

Microangiopathic hemolysisMicroangiopathic hemolysis

Elevated ALT or ASTElevated ALT or AST

Persistent headache , visual disturbance ,Persistent headache , visual disturbance ,epigastric painepigastric pain



IV. EclampsiaIV. Eclampsia

Seizures that cannot be attributed to other Seizures that cannot be attributed to other causes in a woman with preeclampsiacauses in a woman with preeclampsia

Seizures are generalizedSeizures are generalized May appear before , during or after labor May appear before , during or after labor

1010% develop after % develop after 4848 hr postpartumhr postpartum



V. Superimposed preeclampsiaV. Superimposed preeclampsia

New onset proteinuria >=New onset proteinuria >= 300300mg/mg/2424 hr inhr in

hypertensive women but no proteinuriahypertensive women but no proteinuria

beforebefore 2020 wkwk

A sudden increase in proteinuria or BP or A sudden increase in proteinuria or BP or

platelet count <platelet count < 100100,,000000 in women within women withhypertension and proteinuria beforehypertension and proteinuria before 2020 wkwk



DiagnosisDiagnosis



Gestational HTGestational HT

Also called transient HT Also called transient HT

Final Dx : after delivery , by exclusionFinal Dx : after delivery , by exclusion

BP : resting BP , Korotkoff phase V isBP : resting BP , Korotkoff phase V is

used to defined diastolic pressureused to defined diastolic pressure

GHT may later develop preeclampsiaGHT may later develop preeclampsia

1010% of eclamptic seizures develop before% of eclamptic seizures develop before

overt proteinuria is identifiedovert proteinuria is identified

BP rise , increase both mother and fetusBP rise , increase both mother and fetusrisksrisks




Described as ³pregnancyDescribed as ³pregnancy--specificspecific

syndrome of reduced organ perfusionsyndrome of reduced organ perfusion

secondary to vasospasm and endothelialsecondary to vasospasm and endothelial

activation´activation´

Proteinuria & glomerular pathologyProteinuria & glomerular pathology

develop late in the course ,develop late in the course ,

pathophysiologic process begin as earlypathophysiologic process begin as earlyas implantationas implantation




Diastolic hypertension >=Diastolic hypertension >= 9595 , increase fetal, increase fetaldeath ratedeath rate 33 foldfold

Worsening proteinuria resulted in increasingWorsening proteinuria resulted in increasing

preterm deliverypreterm delivery Epigastric pain from hepatocellular necrosis ,Epigastric pain from hepatocellular necrosis ,

ischemia and edema that stretches Glissonischemia and edema that stretches Glissoncapsulecapsule

Thrombocytopenia from platelet activation &Thrombocytopenia from platelet activation &aggregation , microangiopathic hemolysisaggregation , microangiopathic hemolysisinduced by severe vasospasminduced by severe vasospasm




Hematuria , Hyperbilirubinemia : indicativeHematuria , Hyperbilirubinemia : indicative

of severe diseaseof severe disease

Cardiac dysfunction , pulm edema ,

Cardiac dysfunction , pulm edema ,obvious IUGR : indicative of severeobvious IUGR : indicative of severe

diseasedisease

Severity of preeclampsia assess by freq &Severity of preeclampsia assess by freq &intensity of abnormalitiesintensity of abnormalities



Risk factorsRisk factors for preeclampsiafor preeclampsia

NulliparousNulliparous

Advanced maternal age Advanced maternal age

Race and ethnicity (genetic predispositionRace and ethnicity (genetic predisposition& envoronmental factor)& envoronmental factor)

Multifetal gestationMultifetal gestation

ObesityObesity BMI >BMI > 3535 kg/mkg/m22



Superimposed preeclampsiaSuperimposed preeclampsia

11. Hypertension (>=. Hypertension (>=140140//9090) is documented) is documented

antecedent to pregnancyantecedent to pregnancy

22. Hypertension is detected before. Hypertension is detected before 2020 wk ,wk ,unless there is GTDunless there is GTD

33. Hypertension persists long after delivery. Hypertension persists long after delivery

Additional previous Hx or family Hx of HT Additional previous Hx or family Hx of HT

End organ damage : LVH , retinal changeEnd organ damage : LVH , retinal change

Risk abruption ,IU

GR , preterm & deathRisk abruption ,IU

GR , preterm & death



Etiology?Etiology?



EtiologyEtiology

Theory account for the observationTheory account for the observation

hypertensive disorder more likely to develophypertensive disorder more likely to develop

in :in :

11. exposed to chorionic villi for first time. exposed to chorionic villi for first time

22. exposed superabundance of chorionic villi. exposed superabundance of chorionic villi

(Twin ,mole)(Twin ,mole)

33. Preexisting vascular disease. Preexisting vascular disease44. Genetic predisposition. Genetic predisposition



EtiologyEtiology

11. Abnormal trophoblastic invasion of uterine. Abnormal trophoblastic invasion of uterine

vesselsvessels

22. Immunological intolerance between. Immunological intolerance between

maternal and fetoplacental tissuesmaternal and fetoplacental tissues

33. Maternal maladaptation to cardiovascular . Maternal maladaptation to cardiovascular

or inflammatory changes of normalor inflammatory changes of normal

pregnancy (vasculopathy)pregnancy (vasculopathy)44. Dietary deficiencies. Dietary deficiencies

55. Genetic influences. Genetic influences



11. Abnormal trophoblastic invasion. Abnormal trophoblastic invasion

Normal implantation , uterine spiralNormal implantation , uterine spiral

arteries undergo extensive remodeling asarteries undergo extensive remodeling as

they are invaded by endovascular they are invaded by endovascular

trophoblaststrophoblasts

Incomplete invasion (decidual vessels ,Incomplete invasion (decidual vessels ,not myometrial vessels) : preeclampsianot myometrial vessels) : preeclampsia



Abnormal trophoblastic invasion Abnormal trophoblastic invasion



Atherosis : pathology Atherosis : pathology

Endothelial damageEndothelial damage

Insudation of plasma constituents into vesselInsudation of plasma constituents into vessel

wallswalls

Proliferation of myointimal cellsProliferation of myointimal cells

Medial necrosisMedial necrosis

Lipid accumulation in myointimal cells &Lipid accumulation in myointimal cells &

macrophagesmacrophages Aneurysmal dilatation Aneurysmal dilatation

Obstruction of spiral arterioleObstruction of spiral arteriole



22. Immunological factors. Immunological factors

Acute graft rejection Acute graft rejection

Impaired formation of blocking antibodiesImpaired formation of blocking antibodies

to placental antigenic sitesto placental antigenic sites Lack of effective immunization in firstLack of effective immunization in first

pregnanciespregnancies

Lower proportion of ThLower proportion of Th11 , Th, Th22 dominancedominance



22. Immunologic factors. Immunologic factors

Increased risk for first conception , newIncreased risk for first conception , newpartner , conception very shortly after partner , conception very shortly after beginning sexual relation (beginning sexual relation (55% if >% if > 1212mo)mo)

Any kind of previous pregnancy Any kind of previous pregnancy(completed , spontaneous miscarriage or (completed , spontaneous miscarriage or elective abortion) protective againstelective abortion) protective againstpreeclampsiapreeclampsia

Tolerate semiTolerate semi--allogenic graft throughallogenic graft throughfather¶s alloantigenfather¶s alloantigen

J. of Reprod Immunology J. of Reprod Immunology 20032003 ( (5959) : ) : 9393--100 100




ILIL1010 regulate s arterial pressure in earlyregulate s arterial pressure in earlyprimate pregnancyprimate pregnancy

ILIL--1010 & TNF& TNF : vasodilation of early: vasodilation of early

pregnancypregnancy

Anti Anti--human ILhuman IL--1010 MAb caused significantMAb caused significantincrease in MAPincrease in MAP

TNFTNF-- alone or combine with ILalone or combine with IL--1010 notnotalter MAPalter MAP

C ytokineC ytokine 2929 ( (2005 2005) ) 176 176--185 185




Serum from preeclamptic pt contains IgGSerum from preeclamptic pt contains IgGautoantibodyautoantibody

Reacts with ATReacts with AT11 receptor receptor

AT AT11--AA induce signaling in vascular cells AA induce signaling in vascular cellsand trophoblastsand trophoblasts

Including APIncluding AP--11 and NFand NF--kB activationkB activation

Results in tissue factor production ,Results in tissue factor production ,reactive oxygen species (ROS)generationreactive oxygen species (ROS)generation

Autoimmunity Reviews Autoimmunity Reviews 44 ((20052005) :) : 6161--6565



33. Vasculopathy & inflammatory. Vasculopathy & inflammatory

Placental factors released by ischemicPlacental factors released by ischemicchangeschanges

Decidua activated , release noxiousDecidua activated , release noxious

agents provoke endothelial cell injuryagents provoke endothelial cell injury

Endothelial cell dysfunctionEndothelial cell dysfunction

Cytokines : TNFCytokines : TNF , IL, IL




Oxidative stress (ROS , free radical) self Oxidative stress (ROS , free radical) self--

propagating lipid peroxides formationpropagating lipid peroxides formation

Generate highly toxic radicals injureGenerate highly toxic radicals injureendothelial cellsendothelial cells

Modify NOModify NO22 productionproduction

Interfere PG balanceInterfere PG balance




Oxidative stress : produce lipidOxidative stress : produce lipid--ladenladen

macrophage foam cellsmacrophage foam cells

Activation of microvascular coagulation : Activation of microvascular coagulation :ThrombocytopeniaThrombocytopenia

Increased capillary permeability :Increased capillary permeability :proteinuria and edemaproteinuria and edema



44. Nutritional factors. Nutritional factors

Dietary taboos : meat , protein , purines ,Dietary taboos : meat , protein , purines ,

fat , dairy products , saltfat , dairy products , salt

Supplement of Zn ,C

a , Mg preventSupplement of Zn ,C

a , Mg preventpreeclampsia ?preeclampsia ?

Fruits & vegetables : antioxidantFruits & vegetables : antioxidant

Ascorbic acid intake < Ascorbic acid intake < 8585 mg/d ,mg/d ,predispose preeclmapsiapredispose preeclmapsia 22 foldfold

Obesity increase risk preeclampsiaObesity increase risk preeclampsia



55. Genetic factors. Genetic factors

Hereditary hypertension, preeclampsia ,Hereditary hypertension, preeclampsia ,

eclampsiaeclampsia

Polygenic inheritancePolygenic inheritance Asso with HLA Asso with HLA--DRDR44

Maternal Ab against fetal anti HLAMaternal Ab against fetal anti HLA--DR IgDR Ig

Heterozygous for angiotensinogen geneHeterozygous for angiotensinogen genevariant Tvariant T235235

Polymorphisms of genes for TNF , ILPolymorphisms of genes for TNF , IL 11 ,,

LymphotoxinLymphotoxin



Genetics of preeclampsiaGenetics of preeclampsia

Familial predispositionFamilial predisposition

AGT(encode angiotensinogen) & NOS AGT(encode angiotensinogen) & NOS 33

(encode nitric oxide synthestase) genes(encode nitric oxide synthestase) genesmutationmutation

C lin Genet C lin Genet 20032003 :: 6464 :: 96 96--103103



Is preeclampsia an infectiousIs preeclampsia an infectiousdisease?disease?

Analyze IgG Ab against HSV Analyze IgG Ab against HSV--22 , CMV ,, CMV ,

EBV , Toxoplasma gondii at first ANCEBV , Toxoplasma gondii at first ANC

Seronegative for HSV

Seronegative for HSV

--22,C

MV

, EBV

,C

MV

, EBV

increased risk preeclampsia (ORincreased risk preeclampsia (OR 11..77 ,,11..66,,

33..55))

Seronegative for Toxo not associated withSeronegative for Toxo not associated with

increase risk preeclampsia (ORincrease risk preeclampsia (OR 11..00))

Ac ta Obstet Gynec ol S c and Ac ta Obstet Gynec ol S c and 20012001 :: 80 80 :: 1036 1036--8 8



PathogenesisPathogenesis

VasospasmVasospasm

Endothelial cell activationEndothelial cell activation

Increased pressor resonsesIncreased pressor resonses

ProstaglandinsProstaglandins

Nitric oxideNitric oxide

EndothelinsEndothelins

Angiogenic factors (VEGF , PIGF) Angiogenic factors (VEGF , PIGF)



PathogenesisPathogenesis

Increased vascular reactivity toIncreased vascular reactivity to

vasopressor vasopressor

Decrease PGI

Decrease PGI22 production by endotheliumproduction by endothelium

Increase TxAIncrease TxA22 secretion by plateletsecretion by platelet

Increased NOIncreased NO22 synth by endotheliumsynth by endothelium

Decrease NODecrease NO22 syntheasesynthease



PathophysiologyPathophysiology

Endothelial damageEndothelial damage

Interstitial leakageInterstitial leakage

Platelet & fibrinogen depositPlatelet & fibrinogen deposit Increase subendothelial a. resistanceIncrease subendothelial a. resistance

Decreased blood flowDecreased blood flow

Ischemia necrosis , hemorrhageIschemia necrosis , hemorrhage Multiorgan involvementMultiorgan involvement



ComplicationsComplications



Cardiovascular systemCardiovascular system

Increase after loadIncrease after load

Preload diminishPreload diminish

Endothelial activation with extravasationEndothelial activation with extravasation Decreased cardiac outputDecreased cardiac output

Hemoconcentration from generalizedHemoconcentration from generalized

vasoconstriction and endothelialvasoconstriction and endothelialdysfynctiondysfynction

Decreased blood volumeDecreased blood volume



Blood and coagulationBlood and coagulation

Thrombocytopenia from platelet activation,Thrombocytopenia from platelet activation,

aggregation & consumptionaggregation & consumption

Increased platelets activating factor &Increased platelets activating factor &thrombopoietinthrombopoietin

Clotting factors decreaseClotting factors decrease

Erythrocytes rapid hemolysis (increaseErythrocytes rapid hemolysis (increaseLDH , schizocyte , MAHA)LDH , schizocyte , MAHA)



Volume homeostasisVolume homeostasis

Decrease plasma levels of renin , AT II ,Decrease plasma levels of renin , AT II ,

aldosteronealdosterone

DOC

increaseDOC

increase Vasopressin normal despite decreasedVasopressin normal despite decreased

plasma osmolalityplasma osmolality

ANP increased ANP increased

Extracellular fluid : edema : endothelialExtracellular fluid : edema : endothelialinjury , reduced oncotic pressureinjury , reduced oncotic pressure



KidneyKidney

RPF & GFR reducedRPF & GFR reduced

Uric acid elevatedUric acid elevated

Creatinine clearance reduced , oliguriaCreatinine clearance reduced , oliguria Diminished urinary Ca due to increasedDiminished urinary Ca due to increased

tubular reabsorptiontubular reabsorption

Urine sodium elevated

Urine sodium elevated

Urine osmolality , U:P Cr , FE Na :Urine osmolality , U:P Cr , FE Na :prerenal mechanismprerenal mechanism



KidneyKidney

Proteinuria : glomerulopathy : increasedProteinuria : glomerulopathy : increased

permeability : albumin , Hb , globulin ,permeability : albumin , Hb , globulin ,transferinstransferins

Anatomical changes : glomeruli enlarge , Anatomical changes : glomeruli enlarge ,

capillary loops dilated & contracted ,capillary loops dilated & contracted ,

endothelial cells swollen fibrils depositendothelial cells swollen fibrils deposit

(glomerular capillary endotheliosis)(glomerular capillary endotheliosis)



KidneyKidney

Renal tubular lesions : degenerativeRenal tubular lesions : degenerative

change , accumulation with castschange , accumulation with casts

ARF from ATN ARF from ATN Oliguria , azotemia induced byOliguria , azotemia induced by

hypovolemiahypovolemia

Preeclampsia with ARF occur in HELLPPreeclampsia with ARF occur in HELLP

syndrome ½ , placental abruptionsyndrome ½ , placental abruption 11//33

Rarely , irreversible renal cortical necrosisRarely , irreversible renal cortical necrosis



Liver Liver

Periportal hemorrhage in liver peripheryPeriportal hemorrhage in liver periphery

Elevated transaminaseElevated transaminase

HELLP syndromeHELLP syndrome Bleeding cause hepatic rupture(mortalityBleeding cause hepatic rupture(mortality

3030%) , subcapsular hematoma%) , subcapsular hematoma

Conservative treatment

Conservative treatment

Recombinant factor VIIaRecombinant factor VIIa



HELLP syndromeHELLP syndrome

No strict definitionNo strict definition

IncidenceIncidence 2020% of severe preeclampsia or % of severe preeclampsia or

eclampsiaeclampsia

Factors contributing to death : includeFactors contributing to death : include

stroke , coagulopathy , ARDS , ARF ,stroke , coagulopathy , ARDS , ARF ,

sepsissepsis

Insufficient evidence : adjunctive steroidInsufficient evidence : adjunctive steroid



BrainBrain

Headache & visual symptoms associatedHeadache & visual symptoms associated

with eclampsiawith eclampsia

Two cerebral pathology relatedTwo cerebral pathology related

11. gross hemorrhage due to ruptured a.. gross hemorrhage due to ruptured a.

caused by severe HTcaused by severe HT

22. more widespread , edema hyperemia ,. more widespread , edema hyperemia ,ischemia , thrombosis & hemorrhageischemia , thrombosis & hemorrhage caused by preeclampsiacaused by preeclampsia



NeuroimagingNeuroimaging

CT : hypodense area in cortex ,CT : hypodense area in cortex ,

correspond to petechial hemorrhage andcorrespond to petechial hemorrhage and

infarctionsinfarctions

Remarkable changes in area of Remarkable changes in area of distribution of posterior cerebral a.distribution of posterior cerebral a.

MRI : hyperperfusion due to vasogenicMRI : hyperperfusion due to vasogenic

edemaedema

Eclampsia :Eclampsia : 2525% were area of infarction% were area of infarction



Cerebral blood flowCerebral blood flow

Transcranial doppler ultrasonographyTranscranial doppler ultrasonography

Preeclampsia : increase perfusionPreeclampsia : increase perfusionpressure , counter by increasepressure , counter by increase

cerebrovascular resistance(net no change)cerebrovascular resistance(net no change) Eclampsia : loss of autoregulation ,Eclampsia : loss of autoregulation ,

hyperperfusion similar to hypertensivehyperperfusion similar to hypertensive

encephalopathyencephalopathy Eclampsia caused by transient loss of Eclampsia caused by transient loss of

cerebrovascular autoregulationcerebrovascular autoregulation



BlindnessBlindness

Visual disturbance common in SPEVisual disturbance common in SPE

It follows eclampsia in >It follows eclampsia in >1010%%

Develop uptoDevelop upto 11 wk or more after deliverywk or more after delivery

Called ³Amaurosis´Called ³Amaurosis´

Extensive ocipital lobe vasogenic edemaExtensive ocipital lobe vasogenic edema

Resolve completely in all caseResolve completely in all case

Rare cerebral infarct or retinal a. ischemiaRare cerebral infarct or retinal a. ischemia

Retinal detach : resolve withinRetinal detach : resolve within 11 wkwk



Cerebral edemaCerebral edema

Widespread vasogenic edemaWidespread vasogenic edema

S&S : Lethargy , confusion , blurred vision,S&S : Lethargy , confusion , blurred vision,

comacoma

Waxed & wanedWaxed & waned

Rx : Manitol , DexamethasoneRx : Manitol , Dexamethasone



Uteroplacental perfusionUteroplacental perfusion

Compromised uteroplacental perfusionCompromised uteroplacental perfusion

from vasospasmfrom vasospasm

Mean diameter of myometrial spiralMean diameter of myometrial spiral

arterioles decreasearterioles decrease

Doppler flow velocity of uterine arteryDoppler flow velocity of uterine artery

RingRing--like : higher in peripheral than inlike : higher in peripheral than in

central vesselscentral vessels

Preeclampsia was higher resistancePreeclampsia was higher resistance



Can we predict preeclampsia?

Can we predict preeclampsia?



PredictionPrediction

Biological , biochemical & biophysicalBiological , biochemical & biophysicalmarkersmarkers

To identify markers of To identify markers of

faulty placentationfaulty placentation

reduced placental perfusion ,reduced placental perfusion ,

endothelial cell activation & dysfunction ,endothelial cell activation & dysfunction ,

activation of coagulationactivation of coagulation

HOW?



Uric acidUric acid

Decreased renal urate excretion inDecreased renal urate excretion in

preeclampsiapreeclampsia

Serum uric acid exceedingSerum uric acid exceeding 55..99 atat 2424 wkwk

(PPV (PPV 3333%)%)

Not useful in differentiating GHT fromNot useful in differentiating GHT frompreeclampsiapreeclampsia



FibronectinFibronectin

Endothelial cell activationEndothelial cell activation

Low sensitivityLow sensitivity 6969%%

Positive predictive vaulesPositive predictive vaules 1212%% Higher levels byHigher levels by 1212 wks (PPV wks (PPV 2929% NPV % NPV

9898%)%)



Coagulation activationCoagulation activation

Thrombocytopenia and plateletThrombocytopenia and platelet

dysfunctiondysfunction

Increased destruction cause plateletIncreased destruction cause platelet

volumes increase (younger platelet)volumes increase (younger platelet)

Preeclampsia : PAIPreeclampsia : PAI--11 increase increasedincrease increased

relative to PAIrelative to PAI--22 because of endothelialbecause of endothelial

cell dysfunctioncell dysfunction



CytokinesCytokines

Released by vascular endothelium &Released by vascular endothelium &

leukocytes , and macrophages &leukocytes , and macrophages &

lymphocytes at decidualymphocytes at decidua

Interleukin , TNFInterleukin , TNF , CRP : inflammatory, CRP : inflammatory

responseresponse

Possibly predictive preeclampsiaPossibly predictive preeclampsia



Fetal DNAFetal DNA

Fetal DNA in maternal serumFetal DNA in maternal serum

At the time endothelial activation , fetal At the time endothelial activation , fetal

cells released into maternal circulationcells released into maternal circulation

Elevations after Elevations after 2828 wk indicate impendingwk indicate impendingdiseasedisease



Placental peptidesPlacental peptides

CorticotropinCorticotropin--releasing hormone , hCG ,releasing hormone , hCG , Activin A , inhibin A Activin A , inhibin A

Variably elevated depend on duration &Variably elevated depend on duration &

severity of preeclampsiaseverity of preeclampsia Overlap with normal pregnancyOverlap with normal pregnancy

VEGF and PIGF : regulate placentalVEGF and PIGF : regulate placental

development , both antagonized by sFltdevelopment , both antagonized by sFlt11 Excessive sFltExcessive sFlt11 , PIGF in, PIGF in 11stst trimester :trimester :

high riskhigh risk



hCGhCG

hCG in second trimester , >hCG in second trimester , > 22..00 MoMMoM

SensitivitySensitivity 2323..77%%

SpecificitySpecificity 8989..44%% Relative riskRelative risk 22..5454

Positive predictive valuePositive predictive value 99..55%%

Negative predictive valueNegative predictive value 9696..66%%

E ndoc rine Reviews , A pril E ndoc rine Reviews , A pril2002 2002 :: 2323 :: 230 230--257 257



Inhibin A and Activin AInhibin A and Activin A

Activin A : control trophoblast Activin A : control trophoblastdifferentiation in first trimester : high indifferentiation in first trimester : high inpreeclampsiapreeclampsia

Inhibin AInhibin A 1515--1919 wk , >wk , > 22..00 MoMMoM SensitivitySensitivity 4848..66%%

SpecificitySpecificity 2323..66%%

Activin A more sensitive than inhibin A at Activin A more sensitive than inhibin A at2121--2525 wkwk

E ndoc rine Reviews , A pril E ndoc rine Reviews , A pril2002 2002 :: 2323 :: 230 230--257 257



VasoactiveVasoactive

Decrease active renin , AT I & I ,Decrease active renin , AT I & I ,

aldosterone , activity of ACE inaldosterone , activity of ACE in 33rdrd trimtrim

AT II infused test : positive at less than AT II infused test : positive at less than 1010

ng/kgng/kg

Ratio inactive urinary kallikrein /urineRatio inactive urinary kallikrein /urine

creatinine atcreatinine at 1616--2020 wk : lower wk : lower 55 fold in whofold in who

developed preeclampsiadeveloped preeclampsia E ndoc rine Reviews , A pril E ndoc rine Reviews , A pril2002 2002 :: 2323 :: 230 230--257 257



Can we prevent preeclampsia?Can we prevent preeclampsia?



PreventionPrevention

Salt restriction : ineffectiveSalt restriction : ineffective

Inappropriate diuretic therapyInappropriate diuretic therapy

Low dietary calcium increased risk GHTLow dietary calcium increased risk GHT

Fish oil capsules : modify abnormal PGFish oil capsules : modify abnormal PGbalance : ineffectivebalance : ineffective

Low dose aspirin (Low dose aspirin (6060mg) : ineffectivemg) : ineffective

Antioxidants : vitamin C & E : reduced Antioxidants : vitamin C & E : reducedendothelial cell activation , reduction inendothelial cell activation , reduction inpreeclampsiapreeclampsia

L ilk i t k & i k fL ilk i t k & i k f



Low milk intake & risk of Low milk intake & risk of preeclampsiapreeclampsia

Case control studyCase control study

Mean milk intake per day in preeclampsiaMean milk intake per day in preeclampsia

< control group< control group

Drinking more thanDrinking more than 55 glasses per day hasglasses per day has

evident protective effect of developingevident protective effect of developing

preeclampsia (odd ratiopreeclampsia (odd ratio 00..11))

E ur J of Obs & Gyn & Repro BioE ur J of Obs & Gyn & Repro Bio 105 105 ( (2002 2002) ) 1111--1414



Calcium supplementCalcium supplement

Reduction in high BP (RRReduction in high BP (RR 00..5858))

The effect greater among women at highThe effect greater among women at highrisk of developing HT and those with lowrisk of developing HT and those with low

baseline dietary calcium (RRbaseline dietary calcium (RR 00..4747 && 00..3838)) Reduction risk of preeclampsia (RRReduction risk of preeclampsia (RR 00..3535))

The effect greatest in women at high riskThe effect greatest in women at high risk

of developing HT and those with lowof developing HT and those with lowbaseline dietary calcium (RRbaseline dietary calcium (RR 00..2222 && 00..2929)) The C oc hrane database of systemati c reviewsThe C oc hrane database of systemati c reviews 2002 2002



Aspirin Aspirin

Significant benefit in reducingSignificant benefit in reducing

preeclampsia (odds ratiopreeclampsia (odds ratio 00..5555))

Baseline risk of preeclampsia in womenBaseline risk of preeclampsia in women

with abnormal uterine a doppler waswith abnormal uterine a doppler was 1616%%

Obs & Gyn Nov Obs & Gyn Nov 20012001 :: 92 92 :: 861861--6 6



Aspirin in historical risk Aspirin in historical risk

Hx risk : Hx preclampsia ,CHT , DM , renalHx risk : Hx preclampsia ,CHT , DM , renaldisease , FH of preeclampsiadisease , FH of preeclampsia

Significant benefit in reducing perinatalSignificant benefit in reducing perinatal

death (ORdeath (OR 00..7979) & preeclampsia (OR) & preeclampsia (OR00..8686))

Reduction in rates of spontaneous pretermReduction in rates of spontaneous pretermbirth (ORbirth (OR 00..8686))

Increase of mean birth weightIncrease of mean birth weight

No increase risk of placental abruptionNo increase risk of placental abruption Obs & Gyn ,JunObs & Gyn ,Jun 20032003 :: 101101 :: 13191319--32 32



Antiplatelet prevent preeclampsia Antiplatelet prevent preeclampsia

For high risk (previous SPE , DM , CHT ,For high risk (previous SPE , DM , CHT ,renal dis , autoimmune disease) :renal dis , autoimmune disease) : 2727%%reduction in risk of preeclampsiareduction in risk of preeclampsia

For mod risk (first preg , mild rise BP noFor mod risk (first preg , mild rise BP noproteinuria , abnormal uterine a doppler,proteinuria , abnormal uterine a doppler,positive roll over test , multiple preg , FHpositive roll over test , multiple preg , FHSPE , teenage) :SPE , teenage) : 1515% reduction% reduction

Started before implantation & trophoblastStarted before implantation & trophoblastinvasion ,crucial time beforeinvasion ,crucial time before 1616 or or 1212 wkwk

The C oc hrane Database of Systemati c ReviewsThe C oc hrane Database of Systemati c Reviews 20032003



Vitamin E supplementVitamin E supplement

Either at high risk of preeclampsia or withEither at high risk of preeclampsia or withestablished preeclampsiaestablished preeclampsia

No difference in risk of stillbirth , neonatalNo difference in risk of stillbirth , neonatal

death , perinatal death , preterm birth ,death , perinatal death , preterm birth ,IUGR & birthweightIUGR & birthweight

Decrease risk of developing clinicalDecrease risk of developing clinicalpreeclampsia (RRpreeclampsia (RR 00..4444) using fixed) using fixed--effecteffectmodels (no diff using randommodels (no diff using random--effectseffectsmodels)models)

The C oc hrane Database of systemati c ReviewsThe C oc hrane Database of systemati c Reviews 2005 2005



Vitamin E supplementVitamin E supplement

Dosage : above recommended dietaryDosage : above recommended dietaryintake of intake of 77 mg of alphamg of alpha--TE (dailyTE (daily 400400 iu or iu or 800800 iu)iu)

GA : no difference in risk of stillbirth ,GA : no difference in risk of stillbirth ,preterm birth ,IUGR & preeclampsiapreterm birth ,IUGR & preeclampsiabetween before tobetween before to 2020 wk and both beforewk and both before& after & after 2020 wkwk

No difference sideNo difference side--effect (acne , transienteffect (acne , transientweakness, skin rash)weakness, skin rash)

The C oc hrane Database of systemati c ReviewsThe C oc hrane Database of systemati c Reviews 2005 2005



Vitamin C supplementVitamin C supplement

No difference in risk of stillbirth , perinatalNo difference in risk of stillbirth , perinataldeath, IUGR , birthweightdeath, IUGR , birthweight

Increase risk of preterm birth (RRIncrease risk of preterm birth (RR 11..3838))

Heterogeneity : Decreased preeclampsiaHeterogeneity : Decreased preeclampsia(RR(RR 00..4747))

Dosage : above RDI of Dosage : above RDI of 6060 mg (mg (500500 ,,

10001000mg)mg) GA : no difference before & after GA : no difference before & after 2020 wkwk

The C oc hrane Database of Systemati c ReviewsThe C oc hrane Database of Systemati c Reviews 2005 2005



Dietary saltDietary salt

Reduce dietary salt intake vs continue aReduce dietary salt intake vs continue a

normal dietnormal diet

No effect in preeclampsia (RRNo effect in preeclampsia (RR 11..1111))

Insuffient evidence for reliable conclusionsInsuffient evidence for reliable conclusionsabout effect of advice to reduce diet saltabout effect of advice to reduce diet salt

The C oc hrane Database of Systemati c reviewsThe C oc hrane Database of Systemati c reviews 2005 2005



Folic acid supplementFolic acid supplement

Reduction in risk of preeclampsia inReduction in risk of preeclampsia in

supplemented groups (supplemented groups ( 200200 ug &ug & 55 mg/d)mg/d)

In low serum folate pregnancy & womenIn low serum folate pregnancy & women

with Hx preeclampsiawith Hx preeclampsia

Odd ratios of preeclampsia no diff Odd ratios of preeclampsia no diff

between receive folicbetween receive folic 200200 ug VSug VS 55 mg/dmg/d

((00..4646 VSVS 00..5959))

P ed & P erinatal E pid P ed & P erinatal E pid 2005 2005:: 1919 :: 112 112--124124




Early prenatal detectionEarly prenatal detection

Antepartum hospital management Antepartum hospital management

Termination of pregnancyTermination of pregnancy Antihypertensive drug therapy Antihypertensive drug therapy

Delayed delivery with SPEDelayed delivery with SPE



11. Early prenatal detection. Early prenatal detection

Early preeclampsia without overt HT :Early preeclampsia without overt HT :

increased surveillanceincreased surveillance

NewNew--onset diastolic BPonset diastolic BP 8181--8989 mmHg or mmHg or

sudden abnormal wt gain (>sudden abnormal wt gain (> 22 lb/wk duringlb/wk during

33rdrd trimester)trimester)

OPD surveillance unless overt HT ,OPD surveillance unless overt HT ,

proteinuria , visual disturbances or proteinuria , visual disturbances or epigastric discomfortepigastric discomfort



22 A t t tA t t t



22. Antepartum management. Antepartum management

Admit if new onset HT , esp persistent or Admit if new onset HT , esp persistent or

worsening HT or develop proteinuriaworsening HT or develop proteinuria

Detail examine : headache , visualDetail examine : headache , visual

disturbances , epigastric pain , weight gaindisturbances , epigastric pain , weight gain

Proteinuria at least everyProteinuria at least every 22 dd

BP qBP q 44 hr , except midnight & morninghr , except midnight & morning

Creatinine , hematocrit , platelets , liver Creatinine , hematocrit , platelets , liver

enzymes.enzymes.

A t t tA t t t



Antepartum management Antepartum management

Evaluate fetal size , AFEvaluate fetal size , AF

Reduced physical activityReduced physical activity

Sedative not prescribedSedative not prescribed

Ample, not excess, protein & calories diet Ample, not excess, protein & calories diet

Sodium & fluid intake not limit or forcedSodium & fluid intake not limit or forced

Further Mg depend on : severity ,Further Mg depend on : severity ,Gestational Age , condition of cervixGestational Age , condition of cervix



PreeclampsiaPreeclampsia--Initial EvaluationInitial EvaluationPreeclampsiaPreeclampsia--Initial EvaluationInitial Evaluation

Serial blood pressure measurementsSerial blood pressure measurements

Urine protein excretionUrine protein excretion

Fetal monitoringFetal monitoring

Tests to rule out HELLP and other Tests to rule out HELLP and other

complications: Hematocrit, platelets, uriccomplications: Hematocrit, platelets, uric

acid, alanine aminotransferase (ALT),acid, alanine aminotransferase (ALT),

aspartate aminotransferase (AST), lacticaspartate aminotransferase (AST), lacticdehydrogenase (LDH)dehydrogenase (LDH)

Chronic HypertensionChronic Hypertension --



Chronic HypertensionChronic Hypertension


Generally, deliver at term, unlessGenerally, deliver at term, unless

superimposed preeclampsia, HELLPsuperimposed preeclampsia, HELLP

syndromesyndrome

Avoid ACE inhibitors (renal failure, Avoid ACE inhibitors (renal failure,

oligohydramnios, pulmonary hypoplasia,oligohydramnios, pulmonary hypoplasia,

IUGR) and atenolol (IUGR)IUGR) and atenolol (IUGR)

P l iP l i M tM tP l iP l i M tM t



PreeclampsiaPreeclampsia--ManagementManagementPreeclampsiaPreeclampsia--ManagementManagement

Seizure prophylaxisSeizure prophylaxis

Blood pressure controlBlood pressure control

DeliveryDelivery

P l iP l i T PT PP l iP l i T PT P



PreeclampsiaPreeclampsia--Term PregnancyTerm PregnancyPreeclampsiaPreeclampsia--Term PregnancyTerm Pregnancy

Delivery is a shortDelivery is a short--term goalterm goal

Induction of labor is appropriate after Induction of labor is appropriate after

maternalmaternal--fetal observation/stabilizationfetal observation/stabilization

Cesarean reserved for standard obstetricCesarean reserved for standard obstetric

indicationsindications

Cesarean may be recommended in casesCesarean may be recommended in cases

of severe preeclampsia where delivery isof severe preeclampsia where delivery isremoteremote

PreeclampsiaPreeclampsia--PretermPretermPreeclampsiaPreeclampsia--PretermPreterm



PreeclampsiaPreeclampsia PretermPreterm

PregnancyPregnancy


PregnancyPregnancy Mild preeclampsiaMild preeclampsia -- expectantexpectant

management is acceptable under certainmanagement is acceptable under certain

conditionsconditions

Close maternalClose maternal--fetal surveillancefetal surveillance

Ability to intervene either if conditions Ability to intervene either if conditions

worsen or if acceptable gestational ageworsen or if acceptable gestational age

reachedreached InIn--hospital vs. home care?hospital vs. home care?

PreeclampsiaPreeclampsia--PretermPretermPreeclampsiaPreeclampsia--PretermPreterm




PregnancyPregnancy


PregnancyPregnancy Severe preeclampsiaSevere preeclampsia -- controversialcontroversial

Delivery for poor maternal condition isDelivery for poor maternal condition is

likely to be necessary over the short termlikely to be necessary over the short term

Sibai has advocated expectantSibai has advocated expectant

management for selected patients tomanagement for selected patients to

attempt to reduce perinatal morbidity andattempt to reduce perinatal morbidity and

mortality due to prematuritymortality due to prematurity

PreeclampsiaPreeclampsia--PretermPreterm




PregnancyPregnancy Expectant management of severeExpectant management of severe

preeclampsia at preterm gestational age:preeclampsia at preterm gestational age:

HospitalizationHospitalization

Magnesium sulfate for seizure prophylaxis, atMagnesium sulfate for seizure prophylaxis, atleast during initial observation periodleast during initial observation period

Blood pressure control to range of Blood pressure control to range of 140140--

155155//9090--105105 (labetalol or nifedipine)(labetalol or nifedipine) Daily assessment of maternalDaily assessment of maternal--fetal conditionfetal condition

PreeclampsiaPreeclampsia--PretermPreterm




PregnancyPregnancy 2424--3434 weeksweeks ± ± corticosteroids for fetalcorticosteroids for fetal

lung maturationlung maturation

2424--3232 weeksweeks ± ± ongoing daily surveillance if ongoing daily surveillance if

stablestable 3333--3434 weeksweeks ± ± deliver after deliver after 4848 hourshours

Deliver for HELLP syndrome, severeDeliver for HELLP syndrome, severe

headache, uncontrolled hypertension,headache, uncontrolled hypertension,eclampsiaeclampsia

33 Termination of pregnancyTermination of pregnancy



33. Termination of pregnancy. Termination of pregnancy

Delivery is the cure for preeclampsiaDelivery is the cure for preeclampsia

Headache , visual disturbances or Headache , visual disturbances or

epigastric pain : indicative convulsionsepigastric pain : indicative convulsions

(imminent eclampsia)(imminent eclampsia)

Oliguria : ominous signOliguria : ominous sign

SPE : objectives to forestall convulsions ,SPE : objectives to forestall convulsions ,

prevent intracranial hemorrhage , &prevent intracranial hemorrhage , &serious vital organ damageserious vital organ damage

Termination of pregnancyTermination of pregnancy



Termination of pregnancyTermination of pregnancy

Preterm : conservative justified in mildPreterm : conservative justified in mild

preeclampsia, closed observation andpreeclampsia, closed observation and

monitoring to complicationsmonitoring to complications

severe preeclampsia : prompt deliverysevere preeclampsia : prompt delivery

vaginal deliveryvaginal delivery

cc--section if indicatedsection if indicated

Induction of labor not harmful to infants ,Induction of labor not harmful to infants ,but unsuccessfulbut unsuccessful 3535%%



44 Antihypertensive drugAntihypertensive drug



44. Antihypertensive drug. Antihypertensive drug

To prolong pregnancy , or modify perinatalTo prolong pregnancy , or modify perinatal

outcomesoutcomes

Labetolol :Labetolol :

lower mean BP,lower mean BP,

no difference : mean pregnancy prolongation ,no difference : mean pregnancy prolongation ,

birthweight , c/s ratebirthweight , c/s rate

IUGRIUGR 22 foldfold

Antihypertensive drugAntihypertensive drug



Antihypertensive drug Antihypertensive drug

RCT :RCT : blocker (Labetolol) , calciumblocker (Labetolol) , calcium

channel blockers (Nifedipine , Isradipine)channel blockers (Nifedipine , Isradipine)

no benefitno benefit

MetaMeta--analysis : treatment inducedanalysis : treatment induceddecrease maternal BP , may adverselydecrease maternal BP , may adversely

affect fetal growthaffect fetal growth

Prophylactic atenolol decrease incidenceProphylactic atenolol decrease incidencepreeclampsiapreeclampsia

Antihypertensive drugAntihypertensive drug



Antihypertensive drug Antihypertensive drug

ACE Inhibitor should avoid in ACE Inhibitor should avoid in 22ndnd && 33rdrd

trimester trimester

Complication : oligohydram , IUGR , bonyComplication : oligohydram , IUGR , bony

malformations , limb contractures ,malformations , limb contractures ,persistent PDA , pulm hypoplasia , RDS ,persistent PDA , pulm hypoplasia , RDS ,prolonged neonatal hypotension , neonatalprolonged neonatal hypotension , neonataldeathdeath

Early preg taken ACE Inhb : discontinuedEarly preg taken ACE Inhb : discontinuedas soon as possibleas soon as possible



NicardipineNicardipine

Nicardipine startNicardipine start 33 mg/hr ,titrate , maxmg/hr ,titrate , max 33--99mg/hr mg/hr

Target DBP <Target DBP < 100100 or <or < 9090 in HELLPin HELLP

syndrome ptsyndrome pt Median time to obtained targetMedian time to obtained target 2323 minmin

Delivery postponedDelivery postponed 44..77 daysdays

Potential use for second line drug whenPotential use for second line drug whenother antiHT drugs failedother antiHT drugs failed J. of hypertension : Dec J. of hypertension : Dec 2005 2005 :: 2323 :: 23192319--20 20



55. Delayed delivery with. Delayed delivery with



y yy ySuperimposed Pre Eclampsia (SPE)Superimposed Pre Eclampsia (SPE)

SPE remote from termSPE remote from term

Conservative or expectant management inConservative or expectant management in

selected groupselected group SibaiSibai 19851985 : SPE: SPE 1818--2727 wk : perinatalwk : perinatal

mortalitymortality 8787% , no mothers died , placental% , no mothers died , placentalabruption eclampsia , consumptiveabruption eclampsia , consumptivecoagulopathy , RF , encephalopathy ,coagulopathy , RF , encephalopathy ,intracerebral hemorrhage , rupturedintracerebral hemorrhage , rupturedhepatic hematomahepatic hematoma





SibaiSibai 19941994 : SPE: SPE 2828--3232 wk (excludewk (excludeHELLP) : prolonged mean of HELLP) : prolonged mean of 1515..44 d :d :sustainedsustained 44% placental abruption% placental abruption

Abramovici Abramovici 19991999 :: better neonatal outcomes in SPE ,better neonatal outcomes in SPE ,

IUGR not relate to severity of disease ,IUGR not relate to severity of disease ,

IUGR affected survival infants ,IUGR affected survival infants ,

median elapsed timemedian elapsed time 00 ,, 11 ,, 22 days in HELLP ,days in HELLP ,partial , & SPEpartial , & SPE





VigilVigil 20032003 : bed rest , MgSO: bed rest , MgSO4 484 48 hr , bolushr , bolus

antihypertensive drug , volume expansion,antihypertensive drug , volume expansion,

& Dexa& Dexa

Indications for delivery : uncontrollable BP,Indications for delivery : uncontrollable BP,fetal distress , placental abruption , renalfetal distress , placental abruption , renal

failure, HELLP synd , persistent symptomfailure, HELLP synd , persistent symptom

Average pregnancy prolong Average pregnancy prolong 88dd No maternal deaths,No maternal deaths, 66 stillbirth ,stillbirth , 1111

placental abruption ,placental abruption , 2828 IUGRIUGR

Intervention VS ExpectantIntervention VS Expectant



Intervention VS ExpectantIntervention VS Expectant

Insufficient data for reliable conclusions onInsufficient data for reliable conclusions on

maternal outcomematernal outcome

For baby : insufficient reliable conclusionsFor baby : insufficient reliable conclusions

on stillbirth or death after delivery (RRon stillbirth or death after delivery (RR11..5050))

More RDS (RRMore RDS (RR 22..33) , NEC (RR) , NEC (RR55..55))

Less likely to SGA (RRLess likely to SGA (RR 00..3636))

The C oc hrane Database of Systemati c ReviewsThe C oc hrane Database of Systemati c Reviews 2002 2002



EclampsiaEclampsia



EclampsiaEclampsia

Appear before, during or after labor Appear before, during or after labor

Most common in last trimester Most common in last trimester

Shift in incidence toward postpartumShift in incidence toward postpartum

Usually begin in facial twitch , entire bodyUsually begin in facial twitch , entire body

rigid , generalized muscle contraction , jawrigid , generalized muscle contraction , jawopen & close violentlyopen & close violently

Diaphragm fixed , resp halted , then longDiaphragm fixed , resp halted , then longdeep stertorous inhalationdeep stertorous inhalation



EclampsiaEclampsia



EclampsiaEclampsia

Duration of coma variableDuration of coma variable

Hypercarbia , lactic acidemia , fetal bradyHypercarbia , lactic acidemia , fetal bradycardiacardia

High fever High fever ProteinuriaProteinuria

Diminished urine output , hemoglobinuriaDiminished urine output , hemoglobinuria

Pronounced edemaPronounced edema Proteinuria & edema disappear withinProteinuria & edema disappear within 11 wkwk

BP return within a few days toBP return within a few days to 22 wk PPwk PP

EclampsiaEclampsia



EclampsiaEclampsia

Pulmonary edema from aspirationPulmonary edema from aspiration

pneumonitis or heart failurepneumonitis or heart failure

Death from massive cerebral hemorrhageDeath from massive cerebral hemorrhage

Hemiplegia from sublethal hemorrhageHemiplegia from sublethal hemorrhage

Blindness from retinal detachment or Blindness from retinal detachment or

occipital lobe ischemia & edemaoccipital lobe ischemia & edema

Persistent coma due to uncal herniationPersistent coma due to uncal herniation

Rarely eclampsia followed by psychosisRarely eclampsia followed by psychosis

EclampsiaEclampsia



EclampsiaEclampsia

Differential diagnosis : epilepsy ,Differential diagnosis : epilepsy ,

encephalitis , meningitis , cerebral tumor ,encephalitis , meningitis , cerebral tumor ,

cysticercosis , ruptured cerebral aneurysmcysticercosis , ruptured cerebral aneurysm

Prognosis always seriousPrognosis always serious

66% of Maternal death relate to eclampsia% of Maternal death relate to eclampsia

Among PIH patient , maternal death Among PIH patient , maternal death 1616%%

TreatmentTreatment



TreatmentTreatment

11. control of convulsions using IV MgSO. control of convulsions using IV MgSO44

22. Intermittent IV or oral of antihypertensive. Intermittent IV or oral of antihypertensive

drug to lower Diastolic BP <drug to lower Diastolic BP <100100

33. Avoidance of diuretics , limit IV fluid. Avoidance of diuretics , limit IV fluid

adminstration , avoid hyperosmotic agentsadminstration , avoid hyperosmotic agents

44. Delivery. Delivery

Continuous IV regimenContinuous IV regimen



Continuous IV regimenContinuous IV regimen

44--66 gm MgSOgm MgSO44 dilute indilute in 100100 ml fluid , adminml fluid , admin

over over 1515--2020 minmin

BeginBegin 22 g/hr ing/hr in 100100 ml IV maintenanceml IV maintenance

Measure Mg level atMeasure Mg level at 44--66 hr , adjust levelhr , adjust level

betweenbetween 44--77 mEq/LmEq/L

MgSOMgSO44 discontinueddiscontinued 2424 hr after deliveryhr after delivery



MgSOMgSO44



Effective anticonvulsant without producingEffective anticonvulsant without producingCNS depression in either mother or infantCNS depression in either mother or infant

Not given to treat HTNot given to treat HT

Exert specific on cerebral cortexExert specific on cerebral cortex

1010--1515% after MgSO% after MgSO44 : subsequent: subsequentconvulsionconvulsion

Sodium amobarbital & thiopental , if Sodium amobarbital & thiopental , if

excessive agitate in postconvulsion stateexcessive agitate in postconvulsion state In Eclampsia , admin for In Eclampsia , admin for 2424 hr after onsethr after onset

of convulsionof convulsion

M SOM SO44



MgSOMgSO44

Almost totally cleared by renal excretion Almost totally cleared by renal excretion

Monitor urine output , DTR , RRMonitor urine output , DTR , RR

Maintained levelMaintained level 44--77 mEq/LmEq/L

IM & IV regimen , no significant differenceIM & IV regimen , no significant differenceMg levelMg level

MgMg 1010 mEq/L : patellar reflex disappear mEq/L : patellar reflex disappear

>> 1010 mEq/L : respiratory depressionmEq/L : respiratory depression >> 1212 mEq/L : respiratory paralysis & arrestmEq/L : respiratory paralysis & arrest

Cr >Cr >11..33 : half dose MgSO: half dose MgSO44

MgSOMgSO44



MgSOMgSO44

Acute cardiovascular effect Acute cardiovascular effect

Decrease MAPDecrease MAP

Increase COIncrease CO 1313%%

Decrease SVRDecrease SVR

Transient nausea & flushingTransient nausea & flushing

Persist for onlyPersist for only 1515 minmin

MgSOMgSO44



Uterine effectsUterine effects

Depress myometrial contractilityDepress myometrial contractility

Inh calcium entry to myometrial cellInh calcium entry to myometrial cell

Dose dependent : at leastDose dependent : at least 88--1010 mEq/LmEq/L

No uterine effect , when given for No uterine effect , when given for

prophylaxis eclampsia (oxytocinprophylaxis eclampsia (oxytocin

stimulation of labor , admit to deliverystimulation of labor , admit to deliveryintervals , route of delivery)intervals , route of delivery)

MgSOMgSO44



gg

Fetal effectsFetal effects

Promptly cross placentaPromptly cross placenta

Neonatal depression occurs only if severeNeonatal depression occurs only if severe

hypermagnesemia at deliveryhypermagnesemia at delivery Dec rease in beat Dec rease in beat--toto--beat variability beat variability

Possible protective effect against cerebral palsyPossible protective effect against cerebral palsy

in VLBW infantsin VLBW infants

Substantial gross motor dysfunction reducedSubstantial gross motor dysfunction reduced

No serious harmful effectsNo serious harmful effects

Compared with anticonvulsantsCompared with anticonvulsants



Compared with anticonvulsantsCompared with anticonvulsants

MgSOMgSO44 reduce recurrent szreduce recurrent sz 5050%%

compared to diazepam , reduce maternalcompared to diazepam , reduce maternal

& perinatal morbidity (not sig)& perinatal morbidity (not sig)

Maternal mortality reduced compared toMaternal mortality reduced compared tophenytoin (not sig) , less neonatalphenytoin (not sig) , less neonatal

intubation & NICU admissionintubation & NICU admission

Prevent eclamptic sz superior to phenytoinPrevent eclamptic sz superior to phenytoin Lower risk placental abruptionLower risk placental abruption

MgSOMgSO44 & other anticonvulsant& other anticonvulsant



gSOgSO & ot e a t co u sa t& ot e a t co u sa t

Compared with placeboCompared with placebo

Reduce risk eclampsia (RRReduce risk eclampsia (RR 00..4141))

Reduce risk of dying (RRReduce risk of dying (RR 00..5656))

More Side effect (flushing) (More Side effect (flushing) (2424% VS% VS 55%)%) Reduce risk placental abruption (RRReduce risk placental abruption (RR 00..6464))

55% Increase risk c/s% Increase risk c/s

No difference in stillbirth or neonatal deathNo difference in stillbirth or neonatal death(RR(RR 11..0404))


MgSOMgSO44 & other anticonvulsant& other anticonvulsant



gg

Compared to phenytoinCompared to phenytoin

Better Reduce risk of eclampsia (RRBetter Reduce risk of eclampsia (RR 00..0505))

Increase risk c/s (RRIncrease risk c/s (RR 11..2121))

Compared to diazepamCompared to diazepam

Too small for any reliable conclusionsToo small for any reliable conclusions




MgSOMgSO44



MgSOMgSO44

Sz rate in preeclampsia , no szSz rate in preeclampsia , no sz

prophylaxisprophylaxis 33..99%% reduced toreduced to 11..55%%

Mild preeclampsia , estimated risk withoutMild preeclampsia , estimated risk without

prophylaxisprophylaxis 11 inin 100100 , & not asso with, & not asso withsevere maternal morbiditysevere maternal morbidity

Do not given sz prophylaxis in Mild PEDo not given sz prophylaxis in Mild PE

Antihypertensive Antihypertensive



ypyp

Hydralazine suggested if persistentHydralazine suggested if persistent

systolic >systolic > 160160 , or diastolic >, or diastolic > 105105 mmHgmmHg

(NHBPEP(NHBPEP20002000))

55--1010 mg doses atmg doses at 1515--2020 min inervalsmin inervals

Satisfactory response ante or intrapartum :Satisfactory response ante or intrapartum :

diastolicdiastolic 9090--100100

Seldom another antihypertensive neededSeldom another antihypertensive needed FHR deceleration when BP fell toFHR deceleration when BP fell to 110110//8080

Antihypertensives Antihypertensives



ypyp

Labetolol : IV Labetolol : IV 11& nonselective& nonselective --blocker blocker

Lower BP more rapidly , associatedLower BP more rapidly , associated

tachycardiatachycardia

NHBPEP(NHBPEP(20002000) : recommends) : recommends 2020 mg IV mg IV

bolus , if not effective withinbolus , if not effective within 1010 min ,min ,

followed byfollowed by 4040 mg , thenmg , then 8080 mg qmg q 1010 minmin

but not exceedbut not exceed 220220 mg total dose per mg total dose per episode treatedepisode treated




ypyp

NifedipineNifedipine 1010 mg Oral , repeated inmg Oral , repeated in 3030 minmin

, if necessary (NHBPEP, if necessary (NHBPEP 20002000))

Fewer dose required to achieve BP controlFewer dose required to achieve BP control

without increased adverse effectswithout increased adverse effects

Sublingual : potent & rapid :Sublingual : potent & rapid :

cerebrovascular ischemia , MI , conductioncerebrovascular ischemia , MI , conduction

disturbance , deathdisturbance , death Not superior to other hypertensivesNot superior to other hypertensives




ypyp

Verapamil IV Verapamil IV 55--1010 mg/hr mg/hr

Nimodipine IV & oralNimodipine IV & oral

Ketanserin IV (selectiveKetanserin IV (selective 55--HT blocker)HT blocker)

Nitroprusside not recommend unless noNitroprusside not recommend unless no

response , continuous IV , startresponse , continuous IV , start 00..2525

ug/kg/min , increase toug/kg/min , increase to 55 ug/kg/min , fetalug/kg/min , fetal

cyanide toxicity may occur after cyanide toxicity may occur after 44 hr hr

Persistent postpartum HTPersistent postpartum HT



p pp p

HydralazineHydralazine 1010--2525 mg IM qmg IM q 44--66 hr hr

If HT persists or recur : oral labetolol or If HT persists or recur : oral labetolol or

thiazide diuretic are giventhiazide diuretic are given

Two mechanisms :Two mechanisms :

11. Underlying chronic hypertension ,. Underlying chronic hypertension ,

22. Mobilization of edema fluid. Mobilization of edema fluid

Persistent postpartum HTPersistent postpartum HT



p pp p

Atypical syndrome in which SPE Atypical syndrome in which SPE--

eclampsia persists despite deliveryeclampsia persists despite delivery

Single or multiple plasma exchangeSingle or multiple plasma exchange

Plasma exchange performed inPlasma exchange performed in

postpartum women with HELLP syndromepostpartum women with HELLP syndrome

Very few women : persistent HypertensionVery few women : persistent Hypertension

, thrombocytopenia and renal dysfunction, thrombocytopenia and renal dysfunctiondue to thrombotic microangiopathydue to thrombotic microangiopathy

Diuretics & hyperosmotic agentsDiuretics & hyperosmotic agents



yp gyp g

Diuretics : deplete intravascular volume ,Diuretics : deplete intravascular volume ,

compromise placental perfusion , limitedcompromise placental perfusion , limited

used to pulmonary edemaused to pulmonary edema

Hyperosmotic agents : leaks of agentsHyperosmotic agents : leaks of agentsthrough capillaries into lungs & brainthrough capillaries into lungs & brainpromote accumulation of edemapromote accumulation of edema

Fluid therapyFluid therapy



pypy

Lactate Ringers Solution , rateLactate Ringers Solution , rate 6060 ml toml to

125125 ml/hr ml/hr

Unless unusual fluid loss : N/V , diarrhea ,Unless unusual fluid loss : N/V , diarrhea ,

excessive blood lossexcessive blood loss

Oliguria : maternal blood volumeOliguria : maternal blood volume

constricted, admin IV fluid more vigorouslyconstricted, admin IV fluid more vigorously

Women with eclampsia already hasWomen with eclampsia already hasexcessive extracelular fluidexcessive extracelular fluid

Plasma volume expander Plasma volume expander



Plasma volume expansion for treatment of Plasma volume expansion for treatment of

preeclampsiapreeclampsia

Compared colloid with no plasma volumeCompared colloid with no plasma volume

expansionexpansion

Insufficient evidence for any reliable effectInsufficient evidence for any reliable effect


Pulmonary edemaPulmonary edema



Most often do so postpartumMost often do so postpartum

Aspiration should be exclude Aspiration should be exclude

Majority have cardiac failureMajority have cardiac failure

Decrease plasma oncotic pressure , increaseDecrease plasma oncotic pressure , increaseextravascular oncotic pressure , increaseextravascular oncotic pressure , increase

capillary permeability , hemoconcentration ,capillary permeability , hemoconcentration ,

reduced CVP , PCWPreduced CVP , PCWP

Excessive colloid & cyrstalloid cause pulmExcessive colloid & cyrstalloid cause pulmedemaedema

Invasive monitoringInvasive monitoring



Use of pulmonary artery catheterizationUse of pulmonary artery catheterization

Reserved for women with severe cardiacReserved for women with severe cardiac

disease , renal disease , refractorydisease , renal disease , refractory

hypertension , oliguria , pulmonary edemahypertension , oliguria , pulmonary edema

Pulmonary edema by more than onePulmonary edema by more than one

mechanismmechanism

If questionable pulmonary edema :If questionable pulmonary edema :furosemide IV , hydralazine IVfurosemide IV , hydralazine IV

DeliveryDelivery



After eclamptic sz , labor often ensues After eclamptic sz , labor often ensues

spontaneously or can be inducedspontaneously or can be induced

successfully even in remote from termsuccessfully even in remote from term

Because lack of normal pregnancyBecause lack of normal pregnancyhypervolemia , so less tolerant of bloodhypervolemia , so less tolerant of bloodloss at deliveryloss at delivery

Analgesia & anesthesia Analgesia & anesthesia



In the past , SAB , EB were avoidIn the past , SAB , EB were avoid

GA caused by tracheal intubation, suddenGA caused by tracheal intubation, sudden

HT ,pulm edema , intracranial hgeHT ,pulm edema , intracranial hge

Epidural preferred : no serious maternal or Epidural preferred : no serious maternal or fetal complication , lower MAP , Cardiacfetal complication , lower MAP , Cardiacoutput not falloutput not fall

LongLong--term consequenceterm consequence



More prone to hypertensive complicationsMore prone to hypertensive complicationsin future pregnanciesin future pregnancies

Earlier diagnosed , greater recurrenceEarlier diagnosed , greater recurrence

Diagnose beforeDiagnose before 3030 wk , recur wk , recur 4040%% Recurrence rate for women withRecurrence rate for women with 11 episodeepisode

of HELLPof HELLP 55%%

Subsequent preeclampsia , high incidenceSubsequent preeclampsia , high incidenceof preterm , IUGR , placental abruption ,of preterm , IUGR , placental abruption ,c/s deliveryc/s delivery

LongLong--term consequenceterm consequence



Multiparous develop preeclampsia ,Multiparous develop preeclampsia ,

increased risk recur in subsequentincreased risk recur in subsequent

pregnancy compared with nulliparaspregnancy compared with nulliparas

EarlyEarly--onset SPE may have underlyingonset SPE may have underlyingthrombophilias, complicate subsequentthrombophilias, complicate subsequent

pregnanciespregnancies

Preeclampsia not cause chronicPreeclampsia not cause chronichypertensionhypertension



Thank you for your attentionThank you for your attention

Hypertensive Disorder in Pregnancy Untuk Kuliah

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