Hypertensive Disorders in Pregnancy

Scope
 Terminology  Risk

and classification

factors  Etiology  Pathophysiology  Prediction and prevention  Management

Incidence
 3.7

% of pregnancies  16% of pregnancy-related deaths 16% pregnancy Eclampsia 1 in 2000 deliveries

Classification by the working group of the NHBPEP (2000) (2000)

1. Gestational hypertension 2. Chronic hypertension 3. Preeclampsia 4. Eclampsia 5. Preeclampsia superimposed on chronic hypertension (superimposed preeclampsia)

I. Gestational hypertension
 BP

>= 140/90 mmHg for first time during 140/ pregnancy  No proteinuria  BP returns to normal < 12 wk postpartum  Final diagnosis made only postpartum  May have other signs & symptoms of preeclampsia , eg. epigastric discomfort or thrombocytopenia

II. Chronic hypertension

 BP

>= 140/90 mmHg before pregnancy or 140/ diagnosed before 20 wk , not attributable to GTD or  Hypertension first diagnosed after 20 wk and persistent after 12 wk postpartum

Underlying causes of Chronic Hypertension

        

Essential familial hypertension Obesity Arterial abnormalities Endocrine disorders Glomerulonephritis Renoprival hypertension Connective tissue disease PCKD ARF

III. Preeclampsia

Preeclampsia
Mild preeclampsia BP >= 140/90 mmHg after 20 wk gestation 140/ Proteinuria >= 300 mg/24hr or >=1+ dipstick mg/24hr >=1

Severe preeclampsia
Anyone who meets at least two of the following signs:
      

BP >= 160/110 mmHg 160/ Proteinuria 5 g/24hr or >= 2+ dipstick (persistent) g/24hr Cr > 1.2 mg/dl Platelets < 100,000 /mm3 100, /mm3 Microangiopathic hemolysis Elevated ALT or AST Persistent headache , visual disturbance , epigastric pain

IV. Eclampsia
 Seizures  Seizures

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

are generalized  May appear before , during or after labor  10% develop after 48 hr postpartum 10%

V. Superimposed preeclampsia
 New

onset proteinuria >= 300mg/24 hr in 300mg/24 hypertensive women but no proteinuria before 20 wk  A sudden increase in proteinuria or BP or platelet count < 100,000 in women with 100, hypertension and proteinuria before 20 wk

Diagnosis

Gestational HT
 Also

called transient HT  Final Dx : after delivery , by exclusion  BP : resting BP , Korotkoff phase V is used to defined diastolic pressure  GHT may later develop preeclampsia  10% of eclamptic seizures develop before 10% overt proteinuria is identified  BP rise , increase both mother and fetus risks

Preeclampsia
 Described

as pregnancy-specific pregnancysyndrome of reduced organ perfusion secondary to vasospasm and endothelial activation  Proteinuria & glomerular pathology develop late in the course , pathophysiologic process begin as early as implantation

Preeclampsia
  

Diastolic hypertension >= 95 , increase fetal death rate 3 fold Worsening proteinuria resulted in increasing preterm delivery Epigastric pain from hepatocellular necrosis , ischemia and edema that stretches Glisson capsule Thrombocytopenia from platelet activation & aggregation , microangiopathic hemolysis induced by severe vasospasm

Preeclampsia
 Hematuria

, Hyperbilirubinemia : indicative of severe disease  Cardiac dysfunction , pulm edema , obvious IUGR : indicative of severe disease  Severity of preeclampsia assess by freq & intensity of abnormalities

Risk factors for preeclampsia

 Nulliparous  Advanced

maternal age  Race and ethnicity (genetic predisposition & envoronmental factor)  Multifetal gestation  Obesity  BMI > 35 kg/m2

Superimposed preeclampsia
1. Hypertension (>=140/90) is documented (>=140/90) antecedent to pregnancy 2. Hypertension is detected before 20 wk , unless there is GTD 3. Hypertension persists long after delivery Additional previous Hx or family Hx of HT End organ damage : LVH , retinal change Risk abruption , IUGR , preterm & death

Etiology?

Etiology
Theory account for the observation hypertensive disorder more likely to develop in : 1. exposed to chorionic villi for first time 2. exposed superabundance of chorionic villi (Twin ,mole) 3. Preexisting vascular disease 4. Genetic predisposition

Etiology
1. Abnormal trophoblastic invasion of uterine vessels 2. Immunological intolerance between maternal and fetoplacental tissues 3. Maternal maladaptation to cardiovascular or inflammatory changes of normal pregnancy (vasculopathy) 4. Dietary deficiencies 5. Genetic influences

1. Abnormal trophoblastic invasion

 Normal

implantation , uterine spiral arteries undergo extensive remodeling as they are invaded by endovascular trophoblasts  Incomplete invasion (decidual vessels , not myometrial vessels) : preeclampsia

Abnormal trophoblastic invasion

Atherosis : pathology
      

Endothelial damage Insudation of plasma constituents into vessel walls Proliferation of myointimal cells Medial necrosis Lipid accumulation in myointimal cells & macrophages Aneurysmal dilatation Obstruction of spiral arteriole

2. Immunological factors
 Acute

graft rejection  Impaired formation of blocking antibodies to placental antigenic sites  Lack of effective immunization in first pregnancies  Lower proportion of Th1 , Th2 dominance Th1 Th2

2. Immunologic factors
 Increased

risk for first conception , new partner , conception very shortly after beginning sexual relation (5% if > 12mo) (5 12mo)  Any kind of previous pregnancy (completed , spontaneous miscarriage or elective abortion) protective against preeclampsia  Tolerate semi-allogenic graft through semifathers alloantigen


J. of Reprod Immunology 2003 (59) : 93-100 59) 93-

2. Immunological factors
 IL10 IL10

regulate s arterial pressure in early primate pregnancy  IL-10 & TNF : vasodilation of early ILpregnancy  Anti-human IL-10 MAb caused significant AntiILincrease in MAP  TNF- alone or combine with IL-10 not TNFILalter MAP


Cytokine 29 (2005) 176-185 2005) 176-

2. Immunological factors
 Serum

from preeclamptic pt contains IgG autoantibody  Reacts with AT1 receptor AT1  AT1-AA induce signaling in vascular cells AT1 and trophoblasts  Including AP-1 and NF-kB activation APNF Results in tissue factor production , reactive oxygen species (ROS)generation


Autoimmunity Reviews 4 (2005) : 61-65 2005) 61-

3. Vasculopathy & inflammatory

 Placental

factors released by ischemic

changes  Decidua activated , release noxious agents provoke endothelial cell injury  Endothelial cell dysfunction  Cytokines : TNF , IL

3. Vasculopathy & inflammatory

 Oxidative

stress (ROS , free radical) selfselfpropagating lipid peroxides formation  Generate highly toxic radicals injure endothelial cells  Modify NO2 production NO2  Interfere PG balance

3. Vasculopathy & inflammatory

 Oxidative

stress : produce lipid-laden lipidmacrophage foam cells  Activation of microvascular coagulation : Thrombocytopenia  Increased capillary permeability : proteinuria and edema

4. Nutritional factors
 Dietary

taboos : meat , protein , purines , fat , dairy products , salt  Supplement of Zn , Ca , Mg prevent preeclampsia ?  Fruits & vegetables : antioxidant  Ascorbic acid intake < 85 mg/d , predispose preeclmapsia 2 fold  Obesity increase risk preeclampsia

5. Genetic factors
 Hereditary

hypertension, preeclampsia ,

eclampsia  Polygenic inheritance  Asso with HLA-DR4 HLA-DR4  Maternal Ab against fetal anti HLA-DR Ig HLA Heterozygous for angiotensinogen gene variant T235 T235  Polymorphisms of genes for TNF , IL 1 , Lymphotoxin

Genetics of preeclampsia
 Familial

predisposition  AGT(encode angiotensinogen) & NOS 3 (encode nitric oxide synthestase) genes mutation

Clin Genet 2003 : 64 : 96-103 96-

Is preeclampsia an infectious disease?

 Analyze

IgG Ab against HSV-2 , CMV , HSVEBV , Toxoplasma gondii at first ANC  Seronegative for HSV-2, CMV , EBV HSVincreased risk preeclampsia (OR 1.7 ,1.6, 3 .5)  Seronegative for Toxo not associated with increase risk preeclampsia (OR 1.0)


Acta Obstet Gynecol Scand 2001 : 80 : 1036-8 1036-

Pathogenesis
 Vasospasm  Endothelial
    

cell activation

Increased pressor resonses Prostaglandins Nitric oxide Endothelins Angiogenic factors (VEGF , PIGF)

Pathogenesis
 Increased

vascular reactivity to vasopressor  Decrease PG I2 production by endothelium  Increase TxA2 secretion by platelet  Increased NO2 synth by endothelium  Decrease NO2 synthease

Pathophysiology
 Endothelial

damage  Interstitial leakage  Platelet & fibrinogen deposit  Increase subendothelial a. resistance  Decreased blood flow  Ischemia necrosis , hemorrhage  Multiorgan involvement

Complications

Cardiovascular system
 Increase

after load  Preload diminish  Endothelial activation with extravasation  Decreased cardiac output  Hemoconcentration from generalized vasoconstriction and endothelial dysfynction  Decreased blood volume

Blood and coagulation

 Thrombocytopenia

from platelet activation, aggregation & consumption  Increased platelets activating factor & thrombopoietin  Clotting factors decrease  Erythrocytes rapid hemolysis (increase LDH , schizocyte , MAHA)

Volume homeostasis
 Decrease

plasma levels of renin , AT II , aldosterone  DOC increase  Vasopressin normal despite decreased plasma osmolality  ANP increased  Extracellular fluid : edema : endothelial injury , reduced oncotic pressure

Kidney
 RPF

& GFR reduced  Uric acid elevated  Creatinine clearance reduced , oliguria  Diminished urinary Ca due to increased tubular reabsorption  Urine sodium elevated  Urine osmolality , U:P Cr , FE Na : prerenal mechanism

Kidney
 Proteinuria

: glomerulopathy : increased permeability : albumin , Hb , globulin , transferins changes : glomeruli enlarge , capillary loops dilated & contracted , endothelial cells swollen fibrils deposit (glomerular capillary endotheliosis)

 Anatomical

Kidney
 Renal

tubular lesions : degenerative change , accumulation with casts  ARF from ATN  Oliguria , azotemia induced by hypovolemia  Preeclampsia with ARF occur in HELLP syndrome , placental abruption 1/3  Rarely , irreversible renal cortical necrosis

Liver
 Periportal  Elevated

hemorrhage in liver periphery

transaminase  HELLP syndrome  Bleeding cause hepatic rupture(mortality 30%) 30%) , subcapsular hematoma  Conservative treatment  Recombinant factor VIIa

HELLP syndrome
 No

strict definition  Incidence 20% of severe preeclampsia or 20% eclampsia  Factors contributing to death : include stroke , coagulopathy , ARDS , ARF , sepsis  Insufficient evidence : adjunctive steroid

Brain
 Headache

& visual symptoms associated with eclampsia  Two cerebral pathology related 1. gross hemorrhage due to ruptured a. caused by severe HT 2. more widespread , edema hyperemia , ischemia , thrombosis & hemorrhage caused by preeclampsia

Neuroimaging
 CT

: hypodense area in cortex , correspond to petechial hemorrhage and infarctions  Remarkable changes in area of distribution of posterior cerebral a.
 MRI

: hyperperfusion due to vasogenic edema  Eclampsia : 25% were area of infarction 25%

Cerebral blood flow

 Transcranial

doppler ultrasonography  Preeclampsia : increase perfusion pressure , counter by increase cerebrovascular resistance(net no change)  Eclampsia : loss of autoregulation , hyperperfusion similar to hypertensive encephalopathy  Eclampsia caused by transient loss of cerebrovascular autoregulation

Blindness
 Visual

disturbance common in SPE  It follows eclampsia in >10% >10%  Develop upto 1 wk or more after delivery  Called Amaurosis  Extensive ocipital lobe vasogenic edema  Resolve completely in all case  Rare cerebral infarct or retinal a. ischemia  Retinal detach : resolve within 1 wk

Cerebral edema
 Widespread

vasogenic edema  S&S : Lethargy , confusion , blurred vision, coma  Waxed & waned  Rx : Manitol , Dexamethasone

Uteroplacental perfusion
 Compromised

uteroplacental perfusion from vasospasm  Mean diameter of myometrial spiral arterioles decrease  Doppler flow velocity of uterine artery  Ring-like : higher in peripheral than in Ringcentral vessels  Preeclampsia was higher resistance

Can we predict preeclampsia?

Prediction
 Biological

, biochemical & biophysical

markers  To identify markers of

   

faulty placentation reduced placental perfusion , endothelial cell activation & dysfunction , activation of coagulation

HOW?

1. Roll-over test Roll2828-32 wk  Abnormally sensitive to infused angiotensin II  Positive predictive value 33% 33%

Uric acid
 Decreased

renal urate excretion in preeclampsia  Serum uric acid exceeding 5.9 at 24 wk (PPV 33%) 33%)  Not useful in differentiating GHT from preeclampsia

Fibronectin
 Endothelial

cell activation  Low sensitivity 69% 69%  Positive predictive vaules 12% 12%  Higher levels by 12 wks (PPV 29% NPV 29% 98%) 98%)

Coagulation activation
 Thrombocytopenia

and platelet

dysfunction  Increased destruction cause platelet volumes increase (younger platelet)  Preeclampsia : PAI-1 increase increased PAIrelative to PAI-2 because of endothelial PAIcell dysfunction

Cytokines
 Released

by vascular endothelium & leukocytes , and macrophages & lymphocytes at decidua  Interleukin , TNF , CRP : inflammatory response  Possibly predictive preeclampsia

Fetal DNA
 Fetal

DNA in maternal serum  At the time endothelial activation , fetal cells released into maternal circulation  Elevations after 28 wk indicate impending disease

Placental peptides
 Corticotropin-releasing Corticotropin-

hormone , hCG ,

Activin A , inhibin A  Variably elevated depend on duration & severity of preeclampsia  Overlap with normal pregnancy  VEGF and PIGF : regulate placental development , both antagonized by sFlt1 sFlt1  Excessive sFlt1 , PIGF in 1st trimester : sFlt1 high risk

hCG
 hCG

in second trimester , > 2.0 MoM  Sensitivity 23.7% 23.  Specificity 89.4% 89.  Relative risk 2.54  Positive predictive value 9.5%  Negative predictive value 96.6% 96.


Endocrine Reviews , April2002 : 23 : 230-257 April2002 230-

Inhibin A and Activin A

 Activin

A : control trophoblast differentiation in first trimester : high in preeclampsia  Inhibin A 15-19 wk , > 2.0 MoM 15 Sensitivity 48.6% 48.  Specificity 23.6% 23.  Activin A more sensitive than inhibin A at 2121-25 wk


Endocrine Reviews , April2002 : 23 : 230-257 April2002 230-

Vasoactive
 Decrease

active renin , AT I & I , aldosterone , activity of ACE in 3rd trim  AT II infused test : positive at less than 10 ng/kg  Ratio inactive urinary kallikrein /urine creatinine at 16-20 wk : lower 5 fold in who 16developed preeclampsia


Endocrine Reviews , April2002 : 23 : 230-257 April2002 230-

Uterine artery doppler

 Impaired

trophoblastic invasion of spiral arteries , leading to reduction in uteroplacental blood flow  8-22 wk , sensitivity 78% , PPV 28% , 78% 28% unreliable in low risk pregnancies  Combined inhibin A & activin A , sensitivity 86% 86%  Combined hCG & AFP , sensitivity 2-40% 40%

Can we prevent preeclampsia?

Prevention
 Salt

restriction : ineffective  Inappropriate diuretic therapy  Low dietary calcium increased risk GHT  Fish oil capsules : modify abnormal PG balance : ineffective  Low dose aspirin (60mg) : ineffective (60mg)  Antioxidants : vitamin C & E : reduced endothelial cell activation , reduction in preeclampsia

Low milk intake & risk of preeclampsia

 Case

control study  Mean milk intake per day in preeclampsia < control group  Drinking more than 5 glasses per day has evident protective effect of developing preeclampsia (odd ratio 0.1)


Eur J of Obs & Gyn & Repro Bio 105 (2002) 11-14 2002) 11-

Calcium supplement
 Reduction

in high BP (RR 0.58) 58)  The effect greater among women at high risk of developing HT and those with low baseline dietary calcium (RR 0.47 & 0.38) 38)  Reduction risk of preeclampsia (RR 0.35) 35)  The effect greatest in women at high risk of developing HT and those with low baseline dietary calcium (RR 0.22 & 0.29) 29)


The Cochrane database of systematic reviews 2002

Aspirin
 Significant

benefit in reducing preeclampsia (odds ratio 0.55) 55)  Baseline risk of preeclampsia in women with abnormal uterine a doppler was 16% 16%

Obs & Gyn Nov 2001 : 92 : 861-6 861-

Aspirin in historical risk

 Hx

risk : Hx preclampsia ,CHT , DM , renal disease , FH of preeclampsia  Significant benefit in reducing perinatal death (OR 0.79) & preeclampsia (OR 79) 0.86) 86)  Reduction in rates of spontaneous preterm birth (OR 0.86) 86)  Increase of mean birth weight  No increase risk of placental abruption


Obs & Gyn ,Jun 2003 : 101 : 1319-32 1319-

Antiplatelet prevent preeclampsia

 19% 19%

reduction in risk of preeclampsia (RR 0.81) 81)  Greater reduction in risk of preeclampsia in aspirin >75 mg/d (RR 0.49 VS RR 0.86) >75 86)  7% reduction in risk of preterm delivery (RR 0.84) 84)  16% reduction in baby deaths (RR 0.84) 16% 84)  8% reduction in SGA babies (RR 0.92) 92)


The Cochrane Database of Systematic Reviews 2003

Antiplatelet prevent preeclampsia

 For

high risk (previous SPE , DM , CHT , renal dis , autoimmune disease) : 27% 27% reduction in risk of preeclampsia  For mod risk (first preg , mild rise BP no proteinuria , abnormal uterine a doppler, positive roll over test , multiple preg , FH SPE , teenage) : 15% reduction 15%  Started before implantation & trophoblast invasion ,crucial time before 16 or 12 wk


The Cochrane Database of Systematic Reviews 2003

Vitamin E supplement
 Either

at high risk of preeclampsia or with established preeclampsia  No difference in risk of stillbirth , neonatal death , perinatal death , preterm birth , IUGR & birthweight  Decrease risk of developing clinical preeclampsia (RR 0.44) using fixed-effect 44) fixedmodels (no diff using random-effects randommodels)


The Cochrane Database of systematic Reviews 2005

Vitamin E supplement
 Dosage

: above recommended dietary intake of 7 mg of alpha-TE (daily 400 iu or alpha800 iu)  GA : no difference in risk of stillbirth , preterm birth ,IUGR & preeclampsia between before to 20 wk and both before & after 20 wk  No difference side-effect (acne , transient sideweakness, skin rash)


The Cochrane Database of systematic Reviews 2005

Vitamin C supplement
 No

difference in risk of stillbirth , perinatal death, IUGR , birthweight  Increase risk of preterm birth (RR 1.38) 38)  Heterogeneity : Decreased preeclampsia (RR 0.47) 47)  Dosage : above RDI of 60 mg (500 , (500 1000mg) 1000mg)  GA : no difference before & after 20 wk


The Cochrane Database of Systematic Reviews 2005

Antioxidant
 39% 39%

reduction in risk of preeclampsia (RR 0.61) 61)  Reduced risk of SGA infant (RR 0.64) 64)  More preterm birth (RR 1.38) 38)  No difference in develop preeclampsia among low & high risk (RR 0.66 & 0.44) 44)  GA : no diff (<20wk VS before & after (<20wk 20wk) 20wk)


The Cochrane Database of systematic Reviews 2005

Dietary salt
 Reduce

dietary salt intake vs continue a normal diet  No effect in preeclampsia (RR 1.11) 11)  Insuffient evidence for reliable conclusions about effect of advice to reduce diet salt

The Cochrane Database of Systematic reviews 2005

Folic acid supplement

 Reduction

in risk of preeclampsia in supplemented groups ( 200 ug & 5 mg/d)  In low serum folate pregnancy & women with Hx preeclampsia  Odd ratios of preeclampsia no diff between receive folic 200 ug VS 5 mg/d (0.46 VS 0.59) 59)


Ped & Perinatal Epid 2005: 19 : 112-124 2005: 112-

Management

Management
 Early

prenatal detection  Antepartum hospital management  Termination of pregnancy  Antihypertensive drug therapy  Delayed delivery with SPE

1. Early prenatal detection

 Early

preeclampsia without overt HT : increased surveillance  New-onset diastolic BP 81-89 mmHg or New81sudden abnormal wt gain (> 2 lb/wk during 3rd trimester)  OPD surveillance unless overt HT , proteinuria , visual disturbances or epigastric discomfort

2. Antepartum management
 Admit

if new onset HT , esp persistent or worsening HT or develop proteinuria  Detail examine : headache , visual disturbances , epigastric pain , weight gain  Proteinuria at least every 2 d  BP q 4 hr , except midnight & morning  Creatinine , hematocrit , platelets , liver enzymes.

Antepartum management
 Evaluate

fetal size , AF  Reduced physical activity  Sedative not prescribed  Ample, not excess, protein & calories diet  Sodium & fluid intake not limit or forced  Further Mg depend on : severity , Gestational Age , condition of cervix

PreeclampsiaPreeclampsia-Initial Evaluation
 Serial

blood pressure measurements  Urine protein excretion  Fetal monitoring  Tests to rule out HELLP and other complications: Hematocrit, platelets, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH)

Chronic Hypertension Management

 Generally,

deliver at term, unless superimposed preeclampsia, HELLP syndrome  Avoid ACE inhibitors (renal failure, oligohydramnios, pulmonary hypoplasia, IUGR) and atenolol (IUGR)

PreeclampsiaPreeclampsia-Management
 Seizure

prophylaxis  Blood pressure control  Delivery

PreeclampsiaPreeclampsia-Term Pregnancy
 Delivery

is a short-term goal short Induction of labor is appropriate after maternalmaternal-fetal observation/stabilization  Cesarean reserved for standard obstetric indications  Cesarean may be recommended in cases of severe preeclampsia where delivery is remote

PreeclampsiaPreeclampsia-Preterm Pregnancy
 Mild

preeclampsia - expectant management is acceptable under certain conditions  Close maternal-fetal surveillance maternal Ability to intervene either if conditions worsen or if acceptable gestational age reached  In-hospital vs. home care? In-

PreeclampsiaPreeclampsia-Preterm Pregnancy
 Severe

preeclampsia - controversial  Delivery for poor maternal condition is likely to be necessary over the short term  Sibai has advocated expectant management for selected patients to attempt to reduce perinatal morbidity and mortality due to prematurity

PreeclampsiaPreeclampsia-Preterm Pregnancy
 Expectant
 

management of severe preeclampsia at preterm gestational age:

Hospitalization Magnesium sulfate for seizure prophylaxis, at least during initial observation period Blood pressure control to range of 140140155/90155/90-105 (labetalol or nifedipine) Daily assessment of maternal-fetal condition maternal-

PreeclampsiaPreeclampsia-Preterm Pregnancy
 24-34 24

weeks corticosteroids for fetal lung maturation

2424-32 weeks ongoing daily surveillance if stable 3333-34 weeks deliver after 48 hours

 Deliver

for HELLP syndrome, severe headache, uncontrolled hypertension, eclampsia

3. Termination of pregnancy
 Delivery

is the cure for preeclampsia  Headache , visual disturbances or epigastric pain : indicative convulsions (imminent eclampsia)  Oliguria : ominous sign  SPE : objectives to forestall convulsions , prevent intracranial hemorrhage , & serious vital organ damage

Termination of pregnancy
 Preterm

: conservative justified in mild preeclampsia, closed observation and monitoring to complications  severe preeclampsia : prompt delivery
 

vaginal delivery c-section if indicated

 Induction

of labor not harmful to infants , but unsuccessful 35% 35%

4. Antihypertensive drug
 To

prolong pregnancy , or modify perinatal outcomes  Labetolol :

 

lower mean BP, no difference : mean pregnancy prolongation , birthweight , c/s rate IUGR 2 fold

Antihypertensive drug
 RCT

: blocker (Labetolol) , calcium channel blockers (Nifedipine , Isradipine) no benefit  Meta-analysis : treatment induced Metadecrease maternal BP , may adversely affect fetal growth  Prophylactic atenolol decrease incidence preeclampsia

Antihypertensive drug
Inhibitor should avoid in 2nd & 3rd trimester  Complication : oligohydram , IUGR , bony malformations , limb contractures , persistent PDA , pulm hypoplasia , RDS , prolonged neonatal hypotension , neonatal death  Early preg taken ACE Inhb : discontinued as soon as possible
 ACE

Nicardipine
 Nicardipine

start 3 mg/hr ,titrate , max 3-9

mg/hr  Target DBP < 100 or < 90 in HELLP syndrome pt  Median time to obtained target 23 min  Delivery postponed 4.7 days  Potential use for second line drug when other antiHT drugs failed


J. of hypertension : Dec 2005 : 23 : 2319-20 2319-

5. Delayed delivery with Superimposed Pre Eclampsia (SPE)

 SPE

remote from term  Conservative or expectant management in selected group  Sibai 1985 : SPE 18-27 wk : perinatal 18mortality 87% , no mothers died , placental 87% abruption eclampsia , consumptive coagulopathy , RF , encephalopathy , intracerebral hemorrhage , ruptured hepatic hematoma

Delayed delivery with SPE

 Sibai

1994 : SPE 28-32 wk (exclude 28HELLP) : prolonged mean of 15.4 d : 15. sustained 4% placental abruption  Abramovici 1999 :
   

better neonatal outcomes in SPE , IUGR not relate to severity of disease , IUGR affected survival infants , median elapsed time 0 , 1 , 2 days in HELLP , partial , & SPE

Delayed delivery with SPE

 Vigil

2003 : bed rest , MgSO4 48 hr , bolus MgSO4 antihypertensive drug , volume expansion, & Dexa  Indications for delivery : uncontrollable BP, fetal distress , placental abruption , renal failure, HELLP synd , persistent symptom  Average pregnancy prolong 8d  No maternal deaths, 6 stillbirth , 11 placental abruption , 28 IUGR

Intervention VS Expectant
 Insufficient

data for reliable conclusions on maternal outcome  For baby : insufficient reliable conclusions on stillbirth or death after delivery (RR 1.50) 50)  More RDS (RR 2.3) , NEC (RR5.5) (RR5  Less likely to SGA (RR 0.36) 36)


The Cochrane Database of Systematic Reviews 2002

Glucocorticoids
 Not

worsen maternal HT  Decrease RDS , improve fetal survival  No evidence : benefit to ameliorate severity of HELLP syndrome  Transient improve hematological lab : platelet counts  2 Maternal death , 18 stillbirth

EclampsiaEclampsia-Management
 Preeclampsia

complicated by generalized tonictonic-clonic convulsions OR  Fatal coma without convulsions also Major complications included placental abruption (10%) , neuro deficit (7%) , (10%) (7 aspiration pneumonia (7%) , pulm edema (7 (5%) , arrest (4%) , ARF (4%) , death (1%) (4 (4 (1

Eclampsia
 Appear

before, during or after labor  Most common in last trimester  Shift in incidence toward postpartum  Usually begin in facial twitch , entire body rigid , generalized muscle contraction , jaw open & close violently
 Diaphragm

fixed , resp halted , then long deep stertorous inhalation

Eclampsia
 Duration

of coma variable  Hypercarbia , lactic acidemia , fetal brady cardia  High fever  Proteinuria  Diminished urine output , hemoglobinuria  Pronounced edema  Proteinuria & edema disappear within 1 wk  BP return within a few days to 2 wk PP

Eclampsia
 Pulmonary

edema from aspiration pneumonitis or heart failure  Death from massive cerebral hemorrhage  Hemiplegia from sublethal hemorrhage  Blindness from retinal detachment or occipital lobe ischemia & edema  Persistent coma due to uncal herniation  Rarely eclampsia followed by psychosis

Eclampsia
 Differential

diagnosis : epilepsy , encephalitis , meningitis , cerebral tumor , cysticercosis , ruptured cerebral aneurysm  Prognosis always serious  6% of Maternal death relate to eclampsia  Among PIH patient , maternal death 16% 16%

Treatment
1. control of convulsions using IV MgSO4 MgSO4 2. Intermittent IV or oral of antihypertensive drug to lower Diastolic BP <100 <100 3. Avoidance of diuretics , limit IV fluid adminstration , avoid hyperosmotic agents 4. Delivery

Continuous IV regimen
4-6 gm MgSO4 dilute in 100 ml fluid , admin MgSO4 over 15-20 min 15Begin 2 g/hr in 100 ml IV maintenance Measure Mg level at 4-6 hr , adjust level between 4-7 mEq/L MgSO4 MgSO4 discontinued 24 hr after delivery

Intermittent intramuscular
 Give

4 g MgSO4 IV , rate not exceed 1 MgSO4 g/min  Follow with 10 g MgSO4 : 5 g injected MgSO4 each buttock through 3 inch long , 20 gauge needle , (add 1 ml of 2% lidocaine)  If convulsions persist after 15 min , give 2 g more IV slowly  Give 5 g MgSO4 IM q 4 hr MgSO4  MgSO4 discontinue 24 hr after delivery MgSO4

MgSO4 MgSO4
 Effective

anticonvulsant without producing CNS depression in either mother or infant  Not given to treat HT  Exert specific on cerebral cortex  10-15% after MgSO4 : subsequent 10-15% MgSO4 convulsion  Sodium amobarbital & thiopental , if excessive agitate in postconvulsion state  In Eclampsia , admin for 24 hr after onset of convulsion

MgSO4 MgSO4
 Almost

totally cleared by renal excretion  Monitor urine output , DTR , RR  Maintained level 4-7 mEq/L  IM & IV regimen , no significant difference Mg level  Mg 10 mEq/L : patellar reflex disappear  > 10 mEq/L : respiratory depression  > 12 mEq/L : respiratory paralysis & arrest  Cr >1.3 : half dose MgSO4 >1 MgSO4

MgSO4 MgSO4
 Acute

cardiovascular effect  Decrease MAP  Increase CO 13% 13%  Decrease SVR  Transient nausea & flushing  Persist for only 15 min

MgSO4 MgSO4
 Uterine

effects  Depress myometrial contractility  Inh calcium entry to myometrial cell  Dose dependent : at least 8-10 mEq/L  No uterine effect , when given for prophylaxis eclampsia (oxytocin stimulation of labor , admit to delivery intervals , route of delivery)

MgSO4 MgSO4
      

Fetal effects Promptly cross placenta Neonatal depression occurs only if severe hypermagnesemia at delivery Decrease in beat-to-beat variability beat-toPossible protective effect against cerebral palsy in VLBW infants Substantial gross motor dysfunction reduced No serious harmful effects

Compared with anticonvulsants

 MgSO4 MgSO4

reduce recurrent sz 50% 50% compared to diazepam , reduce maternal & perinatal morbidity (not sig)  Maternal mortality reduced compared to phenytoin (not sig) , less neonatal intubation & NICU admission  Prevent eclamptic sz superior to phenytoin  Lower risk placental abruption

MgSO4 MgSO4 & other anticonvulsant

 Compared

with placebo  Reduce risk eclampsia (RR 0.41) 41)  Reduce risk of dying (RR 0.56) 56)  More Side effect (flushing) (24% VS 5%) (24%  Reduce risk placental abruption (RR 0.64) 64)  5% Increase risk c/s  No difference in stillbirth or neonatal death (RR 1.04) 04)


The Cochrane Database of Systematic Reviews 2003

MgSO4 MgSO4 & other anticonvulsant

 Compared

to phenytoin  Better Reduce risk of eclampsia (RR 0.05) 05)  Increase risk c/s (RR 1.21) 21)  Compared to diazepam  Too small for any reliable conclusions

The Cochrane Database of Systematic Reviews 2003

MgSO4 MgSO4 & other anticonvulsant

 Compared

to Nimodipine  Lower risk of eclampsia (RR 0.33) 33)  Increase respiratory problem (RR 3.61) 61)  Greater need for additional antihypertensive drugs (RR 1.19) 19)  No difference in morbidity


The Cochrane Database of Systematic Reviews 2003

MgSO4 MgSO4
 Sz

rate in preeclampsia , no sz prophylaxis 3.9% reduced to 1.5%  Mild preeclampsia , estimated risk without prophylaxis 1 in 100 , & not asso with severe maternal morbidity  Do not given sz prophylaxis in Mild PE

Antihypertensive
 Hydralazine

suggested if persistent systolic > 160 , or diastolic > 105 mmHg (NHBPEP2000) (NHBPEP2000)  5-10 mg doses at 15-20 min inervals 15 Satisfactory response ante or intrapartum : diastolic 90-100 90 Seldom another antihypertensive needed  FHR deceleration when BP fell to 110/80 110/

Antihypertensives
 Labetolol

: IV 1& nonselective -blocker  Lower BP more rapidly , associated tachycardia  NHBPEP(2000) : recommends 20 mg IV NHBPEP(2000) bolus , if not effective within 10 min , followed by 40 mg , then 80 mg q 10 min but not exceed 220 mg total dose per episode treated

Antihypertensives
 Nifedipine

10 mg Oral , repeated in 30 min , if necessary (NHBPEP 2000) 2000)  Fewer dose required to achieve BP control without increased adverse effects  Sublingual : potent & rapid : cerebrovascular ischemia , MI , conduction disturbance , death  Not superior to other hypertensives

Antihypertensives
 Verapamil

IV 5-10 mg/hr  Nimodipine IV & oral  Ketanserin IV (selective 5-HT blocker)  Nitroprusside not recommend unless no response , continuous IV , start 0.25 ug/kg/min , increase to 5 ug/kg/min , fetal cyanide toxicity may occur after 4 hr

Persistent postpartum HT
 Hydralazine

10-25 mg IM q 4-6 hr 10 If HT persists or recur : oral labetolol or thiazide diuretic are given  Two mechanisms :
 

1. Underlying chronic hypertension , 2. Mobilization of edema fluid

Persistent postpartum HT
 Atypical

syndrome in which SPESPEeclampsia persists despite delivery  Single or multiple plasma exchange  Plasma exchange performed in postpartum women with HELLP syndrome  Very few women : persistent Hypertension , thrombocytopenia and renal dysfunction due to thrombotic microangiopathy

Diuretics & hyperosmotic agents

 Diuretics

: deplete intravascular volume , compromise placental perfusion , limited used to pulmonary edema  Hyperosmotic agents : leaks of agents through capillaries into lungs & brain promote accumulation of edema

Fluid therapy
 Lactate

Ringers Solution , rate 60 ml to 125 ml/hr  Unless unusual fluid loss : N/V , diarrhea , excessive blood loss  Oliguria : maternal blood volume constricted, admin IV fluid more vigorously  Women with eclampsia already has excessive extracelular fluid

Plasma volume expander

 Plasma

volume expansion for treatment of preeclampsia  Compared colloid with no plasma volume expansion  Insufficient evidence for any reliable effect

The Cochrane Database of Systematic Reviews 1999

Pulmonary edema
   

Most often do so postpartum Aspiration should be exclude Majority have cardiac failure Decrease plasma oncotic pressure , increase extravascular oncotic pressure , increase capillary permeability , hemoconcentration , reduced CVP , PCWP Excessive colloid & cyrstalloid cause pulm edema

Invasive monitoring
 Use

of pulmonary artery catheterization  Reserved for women with severe cardiac disease , renal disease , refractory hypertension , oliguria , pulmonary edema  Pulmonary edema by more than one mechanism  If questionable pulmonary edema : furosemide IV , hydralazine IV

Delivery
 After

eclamptic sz , labor often ensues spontaneously or can be induced successfully even in remote from term  Because lack of normal pregnancy hypervolemia , so less tolerant of blood loss at delivery

Analgesia & anesthesia

 In

the past , SAB , EB were avoid  GA caused by tracheal intubation, sudden HT ,pulm edema , intracranial hge  Epidural preferred : no serious maternal or fetal complication , lower MAP , Cardiac output not fall

LongLong-term consequence
 More

prone to hypertensive complications in future pregnancies  Earlier diagnosed , greater recurrence  Diagnose before 30 wk , recur 40% 40%  Recurrence rate for women with 1 episode of HELLP 5%  Subsequent preeclampsia , high incidence of preterm , IUGR , placental abruption , c/s delivery

LongLong-term consequence
 Multiparous

develop preeclampsia , increased risk recur in subsequent pregnancy compared with nulliparas  Early-onset SPE may have underlying Earlythrombophilias, complicate subsequent pregnancies  Preeclampsia not cause chronic hypertension

Thank you for your attention