Transcript Hypertensive Disorders in Pregnancy

Hypertensive Disorders
in Pregnancy
รองศาสตราจารย์ นายแพทย์ อติวทุ ธ กมุทมาศ
Scope
 Terminology
 Risk
and classification
factors
 Etiology
 Pathophysiology
 Prediction and prevention
 Management
Incidence
 3.7
% of pregnancies
 16% of pregnancy-related deaths
 Eclampsia 1 in 2000 deliveries
Classification
by the working group of the
NHBPEP (2000)
 1.
Gestational hypertension
 2. Preeclampsia
 3. Eclampsia
 4. Preeclampsia superimposed on chronic
hypertension
(superimposed preeclampsia)
 5. Chronic hypertension
Gestational hypertension
 BP
>= 140/90 mmHg for first time during
pregnancy
 No proteinuria
 BP returns to normal < 12 wk postpartum
 Final diagnosis made only postpartum
 May have other S&S of preeclampsia , eg.
epigastric discomfort or thrombocytopenia
Preeclampsia
 Minimum
criteria
 BP >= 140/90 mmHg after 20 wk gestation
 Proteinuria >= 300 mg/24hr or >=1+
dipstick
 Mild
preeclampsia
 Severe preeclampsia
Severe preeclampsia
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BP >= 160/110 mmHg
Proteinuria 5 g/24hr or >= 2+ dipstick (persistent)
Cr > 1.2 mg/dl
Platelets < 100,000 /mm3
Microangiopathic hemolysis
Elevated ALT or AST
Persistent headache , visual disturbance ,
epigastric pain
Eclampsia
 Seizures
that cannot be attributed to other
causes in a woman with preeclampsia
 Seizures
are generalized
 May appear before , during or after labor
 10% develop after 48 hr postpartum
Superimposed preeclampsia
 New
onset proteinuria >= 300mg/24 hr in
hypertensive women but no proteinuria
before 20 wk
 A sudden increase in proteinuria or BP or
platelet count < 100,000 in women with
hypertension and proteinuria before 20 wk
Chronic hypertension
 BP
>= 140/90 mmHg before pregnancy or
diagnosed before 20 wk , not attributable
to GTD or
 Hypertension first diagnosed after 20 wk
and persistent after 12 wk postpartum
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
overt proteinuria is identified
 BP rise , increase both mother and fetus
risks
Preeclampsia
 Described
as “pregnancy-specific
syndrome 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
 Hemoglobinemia
, Hburia ,
Hyperbilirubinemia : indicative of severe
disease
 Cardiac dysfunction , pulm edema ,
obvious IUGR : indicative of severe
disease
 Severity of preeclampsia assess by freq &
intensity of abnormalities
Superimposed preeclampsia
 1.
Hypertension (>=140/90) is documented
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
Underlying causes of CHT
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Essential familial hypertension
Obesity
Arterial abnormalities
Endocrine disorders
Glomerulonephritis
Renoprival hypertension
Connective tissue disease
PCKD
ARF
Risk factors for preeclampsia
 Nulliparous
 Advanced
maternal age
 Race and ethnicity (genetic predisposition
& envoronmental factor)
 Multifetal gestation
 Obesity
 BMI > 35 kg/m2
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
 4. Dietary deficiencies
 5. Genetic influences
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
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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
Placental growth factors : implications
for abnormal placentation
 Placental
growth factors : regulate
vascular endothelial cell and trophoblast
function
 Highly expressed in trophoblasts during
normal pregnancy
 Significantly decreased in preeclampsia
 Asso with placental bed hypoxia &
ischemia (Abnormal placentation)
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J Soc Gyn Investig 2003 : 10 : 178-88
Placental protein 13 (PP-13)
 PP-3
levels slowly increase during
pregnancy
 In 1st trimester , lower than normal were
found in IUGR ,preeclampsia
 In 2nd & 3rd trimester , higher than normal
concentrations were found in
preeclampsia , IUGR , preterm delivery
 Used for assess risk to develop placental
insuff
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Placenta 2004 : 25 : 608-622
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
Immunologic factors
 Increased
risk for first conception , new
partner , conception very shortly after
beginning sexual relation (5% if > 12mo)
 Any kind of previous pregnancy
(completed , spontaneous miscarriage or
elective abortion) protective against
preeclampsia
 Tolerate semi-allogenic graft through
father’s alloantigen
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J. of Reprod Immunology 2003 (59) : 93-100
Immunological factors
 IL10
regulate s arterial pressure in early
primate pregnancy
 IL-10 & TNFα : vasodilation of early
pregnancy
 Anti-human IL-10 MAb caused significant
increase in MAP
 TNF-α alone or combine with IL-10 not
alter MAP
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Cytokine 29 (2005) 176-185
Immunological factors
 Serum
from preeclamptic pt contains IgG
autoantibody
 Reacts with AT1 receptor
 AT1-AA induce signaling in vascular cells
and trophoblasts
 Including AP-1 and NF-kB activation
 Results in tissue factor production ,
reactive oxygen species (ROS)generation
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Autoimmunity Reviews 4 (2005) : 61-65
Vasculopathy & inflammatory
 Placental
factors released by ischemic
changes
 Decidua activated , release noxious
agents provoke endothelial cell injury
 Endothelial cell dysfunction
 Cytokines : TNFα , IL
Vasculopathy & inflammatory
 Oxidative
stress (ROS , free radical) selfpropagating lipid peroxides formation
 Generate highly toxic radicals injure
endothelial cells
 Modify NO2 production
 Interfere PG balance
Vasculopathy & inflammatory
 Oxidative
stress : produce lipid-laden
macrophage foam cells
 Activation of microvascular coagulation :
Thrombocytopenia
 Increased capillary permeability :
proteinuria and edema
Angiogenic growth factors & HT
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HT : disease of inadequate or aberrant
responses to angiogenic growth factors
 Preeclampsia is accompanied by high circulating
levels of soluble VEGF receptor-1 (inactive
complexes with VEGF + plGF)
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High AGF : contribute to peripheral & pulm
edema , microalb , progression of
atherosclerosis
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Angiogenesis 7 : 2004 : 193-201
Prostaglandin
 Platelet
activation : hallmark of SPE
 Platelet PGH synthase 1-derived (PGHS1derived) & TxA2
 Low dose aspirin treatment decreased
platelet aggregation & prevented
thrombosis
 Decrease progesterone during parturition :
sustain parturition
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J of Clin Inv , April 2005 : 115 : 986-995
PS/PC induce preeclampsia
 Phosphatidylserine
(PS) 80% /
Phosphatidylcholine (PC) 20%
 Significant elevation in SBP
 Significant increase in TAT levels
 Significant decrease platelet counts
 Significant increase proteinuria
 Significant reduction in fetal & placental
weight
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Semin Thromb Hemost. Jun2005 : 31 : 34-20
Endothelin-1
 Increased
ET-1 in amniotic fluid & plasma
of infant and mother in preeclampsia
 Asso with abnormal placentation
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J Vet Intern Med. 2005 Jul-Aug : 19 : 594-8
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
Genetic factors
 Hereditary
hypertension, preeclampsia ,
eclampsia
 Polygenic inheritance
 Asso with HLA-DR4
 Maternal Ab against fetal anti HLA-DR Ig
 Heterozygous for angiotensinogen gene
variant T235
 Polymorphisms of genes for TNF , IL 1β ,
Lymphotoxin α
Genetics of preeclampsia
 Familial
predisposition
 AGT(encode angiotensinogen) & NOS 3
(encode nitric oxide synthestase) genes
mutation
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Clin Genet 2003 : 64 : 96-103
Is preeclampsia an infectious
disease?
 Analyze
IgG Ab against HSV-2 , CMV ,
EBV , Toxoplasma gondii at first ANC
 Seronegative for HSV-2, CMV , EBV
increased risk preeclampsia (OR 1.7 ,1.6,
3.5)
 Seronegative for Toxo not associated with
increase risk preeclampsia (OR 1.0)
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Acta Obstet Gynecol Scand 2001 : 80 : 1036-8
Pathogenesis
 Vasospasm
 Endothelial
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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
Comparison of mean ATII infusion doses
required to evoke a pressor response
Pathophysiology
 Endothelial
damage
 Interstitial leakage
 Platelet & fibrinogen deposit
 Increase subendothelial a. resistance
 Decreased blood flow
 Ischemia necrosis , hemorrhage
 Multiorgan involvement
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 plt 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
 Anatomical
changes : glomeruli enlarge ,
capillary loops dilated & contracted ,
endothelial cells swollen fibrils deposit
(glomerular capillary endotheliosis)
Kidney
 Renal
tubular lesions : degenerative
change , accumulation with casts
 ARF from ATN
 Oliguria , azotemia induced by
hypovolemia
 Preeclampsia with ARF occur in HELLP
syndrome ½ , 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%) , subcapsular hematoma
 Conservative treatment
 Recombinant factor VIIa
HELLP syndrome
 No
strict definition
 Incidence 20% of severe preeclampsia or
eclampsia
 Factors contributing to death : include
stroke , coagulopathy , ARDS , ARF ,
sepsis
 Insufficient evidence : adjunctive steroid
Brain
 Headache
& visual symptoms asso 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
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%
 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
central vessels
 Preeclampsia was higher resistance
Prediction
 Biological
, biochemical & biophysical
markers
 To identify markers of
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faulty placentation
reduced placental perfusion ,
endothelial cell activation & dysfunction ,
activation of coagulation
Roll-over test
 28-32
wk
 Abnormally sensitive to infused
angiotensin II
 Positive predictive value 33%
Uric acid
 Decreased
renal urate excretion in
preeclampsia
 Serum uric acid exceeding 5.9 at 24 wk
(PPV 33%)
 Not useful in differentiating GHT from
preeclampsia
Fibronectin
 Endothelial
cell activation
 Low sensitivity 69%
 Positive predictive vaules 12%
 Higher levels by 12 wks (PPV 29% NPV
98%)
Coagulation activation
 Thrombocytopenia
and platelet
dysfunction
 Increased destruction cause platelet
volumes increase (younger platelet)
 Preeclampsia : PAI-1 increase increased
relative to PAI-2 because of endothelial
cell dysfunction
Oxidative stress
 Increased
levels of lipid peroxides
 Prooxidants : iron , transferin , ferritin , TG
, FFA , lipoprotein
 Antioxidants : ascorbic acid , vitamin E
 Hyperhomocysteinemia in mid pregnancy
risk for atherosclerosis , 3-4 fold risk
preeclampsia , influenced by folic acid
supplement
Cytokines
 Released
by vascular endothelium &
leukocytes , and macrophages &
lymphocytes at decidua
 Interleukin , TNF α , CRP : inflammatory
response
 Possibly predictive preeclampsia
Placental peptides
 Corticotropin-releasing
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
 Excessive sFlt1 , PIGF in 1st trimester :
high risk
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
Uterine artery doppler
 Impaired
trophoblastic invasion of spiral
arteries , leading to reduction in
uteroplacental blood flow
 8-22 wk , sensitivity 78% , PPV 28% ,
unreliable in low risk pregnancies
 Combined inhibin A & activin A , sensitivity
86%
 Combined hCG & AFP , sensitivity 2-40%
hCG
 hCG
in second trimester , > 2.0 MoM
 Sensitivity 23.7%
 Specificity 89.4%
 Relative risk 2.54
 Positive predictive value 9.5%
 Negative predictive value 96.6%
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Endocrine Reviews , April2002 : 23 : 230-257
Inhibin A and Activin A
 Activin A :
control trophoblast
differentiation in first trimester : high in
preeclampsia
 Inhibin A 15-19 wk , > 2.0 MoM
 Sensitivity 48.6%
 Specificity 23.6%
 Activin A more sensitive than inhibin A at
21-25 wk
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Endocrine Reviews , April2002 : 23 : 230-257
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
developed preeclampsia
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Endocrine Reviews , April2002 : 23 : 230-257
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
 Antioxidants : vitamin C & E : reduced
endothelial cell activation , reduction in
preeclampsia
Low milk intake risk preeclmpsia
 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)
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Eur J of Obs & Gyn & Repro Bio 105 (2002) 11-14
Calcium supplement
 Reduction
in high BP (RR 0.58)
 The effect greater among women at high
risk of developing HT and those with low
baseline dietary calcium (RR 0.47 & 0.38)
 Reduction risk of preeclampsia (RR 0.35)
 The effect greatest in women at high risk
of developing HT and those with low
baseline dietary calcium (RR 0.22 & 0.29)
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The Cochrane database of systematic reviews 2002
Aspirin
 Significant
benefit in reducing
preeclampsia (odds ratio 0.55)
 Baseline risk of preeclampsia in women
with abnormal uterine a doppler was 16%
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Obs & Gyn Nov 2001 : 92 : 861-6
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
0.86)
 Reduction in rates of spontaneous preterm
birth (OR 0.86)
 Increase of mean birth weight
 No increase risk of placental abruption
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Obs & Gyn ,Jun 2003 : 101 : 1319-32
Antiplatelet prevent preeclampsia
 19%
reduction in risk of preeclampsia (RR
0.81)
 Greater reduction in risk of preeclampsia
in aspirin >75 mg/d (RR 0.49 VS RR 0.86)
 7% reduction in risk of preterm delivery
(RR 0.84)
 16% reduction in baby deaths (RR 0.84)
 8% reduction in SGA babies (RR 0.92)

The Cochrane Database of Systematic Reviews 2003
Antiplatelet prevent preeclampsia
 For
high risk (previous SPE , DM , CHT ,
renal dis , autoimmune disease) : 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
 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
models (no diff using random-effects
models)

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
800 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
weakness, 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)
 Heterogeneity : Decreased preeclampsia
(RR 0.47)
 Dosage : above RDI of 60 mg (500 ,
1000mg)
 GA : no difference before & after 20 wk

The Cochrane Database of Systematic Reviews 2005
Antioxidant
 39%
reduction in risk of preeclampsia (RR
0.61)
 Reduced risk of SGA infant (RR 0.64)
 More preterm birth (RR 1.38)
 No difference in develop preeclampsia
among low & high risk (RR 0.66 & 0.44)
 GA : no diff (<20wk VS before & after
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)
 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)

Ped & Perinatal Epid 2005: 19 : 112-124
Management
 Early
prenatal detection
 Antepartum hospital management
 Termination of pregnancy
 Antihypertensive drug therapy
 Delayed delivery with SPE
Early prenatal detection
 Early
preeclampsia without overt HT :
increased surveillance
 New-onset diastolic BP 81-89 mmHg or
sudden abnormal wt gain (> 2 lb/wk during
3rd trimester)
 OPD surveillance unless overt HT ,
proteinuria , visual disturbances or
epigastric discomfort
Antepartum management
 Admit
if new onset HT , esp persistent or
worsening HT or develop proteinuria
 Detail examine : headache , visual
disturbances , epigastric pain , wt gain
 Wt , OD
 Proteinuria at least every 2 d
 BP q 4 hr , except midnight & morning
 Cr , Hct , plt , liver enz.
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 , GA ,
condition of Cx
Termination of pregnancy
 Delivery
is the cure for preeclampsia
 Headache , visual disturbances or
epigastric pain : indicative convulsions
 Oliguria : ominous sign
 SPE : objectives to forestall convulsions ,
prevent intracranial hemorrhage , &
serious vital organ damage
Termination of pregnancy
 Preterm
: conservative justified in mild
case , F/U NST or BPP
 Mod or severe preeclampsia : prompt
delivery :
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IV oxytocin ,
preinduction withprostaglandin or osmotic
dilator ,
c/s if indicated
 Induction
of labor not harmful to infants ,
but unsuccessful 35%
Antihypertensive drug
 To
prolong pregnancy , or modify perinatal
outcomes
 Labetolol :
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lower mean BP,
no difference : mean pregnancy prolongation ,
birthweight , c/s rate
IUGR 2 fold
Antihypertensive drug
: β blocker (Labetolol) , calcium
channel blockers (Nifedipine , Isradipine)
no benefit
 Meta-analysis : treatment induced
decrease maternal BP , may adversely
affect fetal growth
 Prophylactic atenolol decrease incidence
preeclampsia
 RCT
Antihypertensive drug
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 ACEI : discontinued as
soon as possible
 ACEI
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
Delayed delivery with SPE
 SPE
remote from term
 Conservative or expectant management in
selected group
 Sibai 1985 : SPE 18-27 wk : perinatal
mortality 87% , no mothers died , placental
abruption eclampsia , consumptive
coagulopathy , RF , encephalopathy ,
intracerebral hemorrhage , ruptured
hepatic hematoma
Delayed delivery with SPE
 Sibai
1994 : SPE 28-32 wk (exclude
HELLP) : prolonged mean of 15.4 d :
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
comment
 1.
interval very short
 2. GA difference betw SPE & HELLP
syndrome relate to timing of onset of
disease itself
 3. IUGR prevalent in severe disease ,
adverse affect infant survival
 4. overlook maternal safety
Delayed delivery with SPE
 Vigil
2003 : bed rest , MgSO4 48 hr , bolus
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 Expecntant
 Insufficient
data for reliable conclusions on
maternal outcome
 For baby : insufficient reliable conclusions
on stillbirth or death after delivery (RR
1.50)
 More RDS (RR 2.3) , NEC (RR5.5)
 Less likely to SGA (RR 0.36)

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
Eclampsia
 Preeclampsia
complicated by generalized
tonic-clonic convulsions
 Fatal coma without convulsions also call
 Major complications included placental
abruption (10%) , neuro deficit (7%) ,
aspiration pneumonia (7%) , pulm edema
(5%) , arrest (4%) , ARF (4%) , death (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%
treatment
 1.
control of convulsions using IV MgSO4
 2. Intermittent IV or oral of
antihypertensive drug to lower Diastolic
BP <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 over 15-20 min
 Begin 2 g/hr in 100 ml IV maintenance
 Measure Mg level at 4-6 hr , adjust level
between 4-7 mEq/L
 MgSO4 discontinued 24 hr after delivery
Intermittent intramuscular
 Give
4 g MgSO4 IV , rate not exceed 1
g/min
 Follow with 10 g MgSO4 : 5 g injected
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 discontinue 24 hr after delivery
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
convulsion
 Sodium amobarbital & thiopental , if
excessive agitate in postconvulsion state
 In Eclampsia , admin for 24 hr after onset
of convulsion
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
MgSO4
 Acute
cardiovascular effect
 Decrease MAP
 Increase CO 13%
 Decrease SVR
 Transient nausea & flushing
 Persist for only 15 min
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







Fetal effects
Promptly cross placenta
Neonatal depression occurs only if severe
hypermagnesemia at delivery
Decrease in beat-to-beat variability
Possible protective effect against cerebral palsy
in VLBW infants
Substantial gross motor dysfunction reduced
No serious harmful effects
Compared with anticonvulsants
 MgSO4
reduce recurrent sz 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 & other anticonvulsant
 Compared
with placebo
 Reduce risk eclampsia (RR 0.41)
 Reduce risk of dying (RR 0.56)
 More Side effect (flushing) (24% VS 5%)
 Reduce risk placental abruption (RR 0.64)
 5% Increase risk c/s
 No difference in stillbirth or neonatal death
(RR 1.04)

The Cochrane Database of Systematic Reviews 2003
MgSO4 & other anticonvulsant
 Compared
to phenytoin
 Better Reduce risk of eclampsia (RR 0.05)
 Increase risk c/s (RR 1.21)
 Compared to diazepam
 Too small for any reliable conclusions

The Cochrane Database of Systematic Reviews 2003
MgSO4 & other anticonvulsant
 Compared
to Nimodipine
 Lower risk of eclampsia (RR 0.33)
 Increase respiratory problem (RR 3.61)
 Greater need for additional
antihypertensive drugs (RR 1.19)
 No difference in morbidity

The Cochrane Database of Systematic Reviews 2003
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 MPE
Antihypertensive
 Hydralazine
suggested if persistent
systolic > 160 , or diastolic > 105 mmHg
(NHBPEP2000)
 5-10 mg doses at 15-20 min inervals
 Satisfactory response ante or intrapartum :
diastolic 90-100
 Seldom another antihypertensive needed
 FHR deceleration when BP fell to 110/80
Antihypertensives
: IV α1& nonselective β-blocker
 Lower BP more rapidly , associated
tachycardia
 NHBPEP(2000) : recommends 20 mg IV
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
 Labetolol
Antihypertensives
 Nifedipine
10 mg Oral , repeated in 30 min
, if necessary (NHBPEP 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
 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 SPEeclampsia 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
 LRS
, rate 60 ml to 125 ml/hr
 Unless unusual fluid loss : N/V , diarrhea ,
excessive blood loss
 Oligria : 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
Long-term consequence
 More
prone to hypertensive complications
in future pregnancies
 Earlier diagnosed , greater recurrence
 Diagnose before 30 wk , recur 40%
 Recurrence rate for women with 1 episode
of HELLP 5%
 Subsequent preeclampsia , high incidence
of preterm , IUGR , placental abruption ,
c/s delivery
Long-term consequence
 Multiparous
develop preeclampsia ,
increased risk recur in subsequent
pregnancy compared with nulliparas
 Early-onset SPE may have underlying
thrombophilias , complicate subsequent
pregnancies
 Preeclampsia not cause chronic
hypertension
Thank you for your
attention