PREEKLAMPSIA :

TATA LAKSANA TERKINI

SRI SULISTYOWATI

BAGIAN OBSTETRI DAN GINEKOLOGI

FAKULTAS KEDOKTERAN UNIVERSITAS SEBELAS MARET
SURAKARTA
 HIPERTENSI DALAM
KEHAMILAN

Kronis/ kehamilan dg
<20
hipertensi 
Minggu
Preeklampsia
usia hamil
Superimposed

TD-S> 140 mm Hg
dan atau Organ tidak
TD-D> 90 mm Hg terlibat 
Gestasional
hipertensi
>20 Tanda/ gejala
Minggu klinis dan lab
usia hamil abnormal Preeklampsia,
Sindroma
Hellp,
Eklampsia
 CLASSIFICATION AND
DIAGNOSIS OF PREGNANCY-
ASSOCIATED WITH
HYPERTENSION
 PREEKLAMPSIA

• 2% – 10% DARI
SELURUH
KEHAMILAN
• DI NEGARA
BERKEMBANG 7x
PENYUMBANG > DIBANDING
NEGARA MAJU
UTAMA
KESAKITAN DAN
KEMATIAN IBU DI INDONESIA:
SERTA JANIN • 30% – 40% 
PENYEBAB
KEMATIAN IBU
• 30% – 50% 
PENYEBAB
KEMATIAN JANIN
 PREEKLAMPSIA

RSUD DR. MOEWARDI SURAKARTA

70 63.33
66.66

60 57.14 60.68
50
40
30
30 23
19 21
20 15 14
12 10
10
0
2012 2013 2016 2017
Jumlah Kematian Ibu Preeklampsia
Persentase
COMPLICATIONS OF
PREECLAMPSIA
 RISK FACTORS FOR
PREECLAMPSIA

Risk factors OR or RR (95% Cl)

Antiphospholipid antibody syndrome 9.7 (4.3–21.7)
Renal disease 7.8 (2.2–28.2)
Prior preeclampsia 7.2 (5.8–8.8)
Systemic lupus erythematosus 5.7 (2.0–16.2)
Nulliparity 5.4 (2.8–10.3)
HIV+ HAART treatment 5.6 (1.7–18.1)
HIV positive (untreated) 4.9 (2.4–10.1)
Chronic hypertension 3.8 (3.4–4.3)
Diabetes Mellitus 3.6 (2.5–5.0)
Multiple Gestation 3.5 (3.0–4.2)
Strong family history of cardiovascular disease (heart 3.2 (1.4–7.7)
disease or stroke in ≥2 first degree relatives)
Obesity 2.5 (1.7–3.7)
Family history of preeclampsia in first degree relative 2.3–2.6 (1.8–3.6)
Advanced maternal age (>40) for multiple pregnancy 1.96 (1.34–2.87)
maternal age (>40) for nulliparas Front. Physiol.1.68
9:973.(1.23–2.29)
doi:
10.3389/fphys.2018.00973

Circ Res. 2019;124:1094-1112. DOI:

10.1161/CIRCRESAHA.118.313276
PREEKLAMPSIA
PREEKLAMPSIA

KOMPLIKASI
PADA IBU:
• KEJANG • HIPERTENSI
• HELLP EMERGENSI
SYNDROME • STROKE
• EDEMA • PERSALINAN
PARU PRETERM
• SOLUSIO • PERDARAHAN
PLASENTA
• DIC
PREEKLAMPSIA

KOMPLIKASI PADA JANIN:

 KEMATIAN JANIN DLM
RAHIM
 PERTUMBUHAN JANIN
TERHAMBAT
 GAWAT JANIN
 PREMATURITAS
PREEKLAMPSIA

• PENCEGAHAN :
MENCEGAH
KEHAMILAN
(KONTRASEPSI/ KB)
 PREEKLAMPSIA

• TERAPI DEFINITIF : PERSALINAN

PATHOGENESIS OF
PREECLAMPSIA
MANAGEMENT OF
PREECLAMPSIA
 CLINICAL PRACTICE RECOMMENDATIONS FOR THE PREVENTION AND
MANAGEMENT OF PRE-ECLAMPSIA AND ECLAMPSIA (PE/E)1
During Antenatal Care
 Practices  Practices NOT
Practice Implication
Recommended Recommended
 Calcium  Vitamin D Provide calcium to all
supplementation during supplementation during women with low calcium
pregnancy in areas pregnancy. intake and low-dose
where calcium intake is  Calcium acetylsalicylic acid to
low (<900 mg/day) supplementation during selected groups for the
pregnancy in areas prevention of PE/E.
where calcium While vitamin
deficiency is not supplementation can be
present. useful for other health
conditions, do not provide
 Low-dose  Individual or combined
Vitamins C, D, or E, to
acetylsalicylic acid vitamin C and vitamin
pregnant women as part of a
(aspirin, 75 mg) for the E supplementation.
strategy for prevention of
prevention of pre-
PE/E
eclampsia in women at
high risk of developing
the condition
CLINICAL PRACTICE RECOMMENDATIONS FOR THE PREVENTION
AND MANAGEMENT OF PRE-ECLAMPSIA AND ECLAMPSIA (PE/E)1
During Antenatal Care
 Practices  Practices NOT
Practice Implication
Recommended Recommended
 Antihypertensive  Use of diuretics, Give antihypertensive
drugs for pregnant particularly thiazides, drugs, but not diuretics,
women with severe for prevention of pre- to pregnant women with
hypertension eclampsia and its severe hypertension.
complications
 Advice to rest at Do not advise rest or
home dietary salt restriction for
pregnant women to
 Strict bed rest for prevent pre-eclampsia or
pregnant women with its complications
hypertension (with or
without proteinuria).
 Restriction in dietary
salt intake
CLINICAL PRACTICE RECOMMENDATIONS FOR THE PREVENTION AND
MANAGEMENT OF PRE-ECLAMPSIA AND ECLAMPSIA (PE/E)1
During Antenatal Care
 Practices  Practices NOT
Practice Implication
Recommended Recommended
 In women with severe For a woman with severe
pre-eclampsia, if there preeclampsia during a
is a viable fetus and the preterm
pregnancy is less than pregnancy (< 37 weeks),
37 weeks of gestation, clinicians can monitor the
expectant management woman if: (1) her blood
can be considered, pressure is under control;
provided that (2) there is no fetal distress;
uncontrolled maternal and (3) there are no signs of
hypertension, maternal organ dysfunction.
increasing maternal Continuous
organ dysfunction, and monitoring is necessary
fetal distress do not during this period of
occur and the expectant management
conditions can be
monitored
 During Labor and Birth
 Recommended Practice Implication
Practices
 Induction of labor for Conduct an expedited
women with severe pre- delivery for women with
eclampsia at a gestational severe preeclampsia remote
age when the fetus is not from term, whether or not
viable or is unlikely to the fetus is viable
achieve viability within
one or two weeks
 Expedited delivery for
women with severe pre-
eclampsia at term.
 During Labor and Birth
 Recommended Practices
 Magnesium sulfate, in preference to
other anticonvulsants, for the
prevention of eclampsia in women
with severe preeclampsia
 Magnesium sulfate, in preference to
other anticonvulsants, for treatment of
women with eclampsia
 The full intravenous or intramuscular
magnesium sulfate regimen for the
prevention and treatment of eclampsia
 For women with severe pre-eclampsia
or eclampsia, in settings where it is
not possible to administer the full
magnesium sulfate regimen, use the
magnesium sulfate loading dose
followed by immediate transfer to a
higher-level health care facility
Practice Implication
Magnesium sulfate is the anticonvulsant
of choice for women with severe pre-
eclampsia or eclampsia. If possible,
give a full regimen of magnesium sulfate
to women with eclampsia or severe pre-
eclampsia. If the administration of
a full regimen is not possible, these
women should be given the loading dose
of magnesium sulfate and should be
immediately transferred to a higher-level
health care facility for further treatment
BEBERAPA ALTERNATIF TERAPI PADA PREEKLAMSIA
YANG SUDAH DILAKUKAN META ANALISIS
 MANAGEMENT OF
ECLAMPSIA
• Airway-Breathing-Circulation

• Overcome and prevent seizures / anticonvulsants

• Fluid management

• Controlling blood pressure

• Supporting Examination

• Delivery

• Postpartum care
 FLUID
MANAGEMENT

 Iatrogenic fluid overload 

major cause of maternal death in
preclampsia / eclampsia
 More fluid restriction is
recommended for intrapartum
and postpartum
 80 ml ​/ hour or 1 ml / kg bw/
hour, or urine output in the
previous hour + 30 ml
 Loading 500 ml of crystalloid:
before antihypertensive, epidural
anesthesia, early management of
oliguria
 ANTICONVULSANT/
MAGNESIUM SULFATE
Guidelines Patients eligibility
RCOG In the discussion, they argue that
while benefit has been observed at
more advanced gestations, the
magnitude of effect is likely to be
largest at earliest gestations and
limitation of resources makes an
upper limit of 30 weeks a
pragmatic choice. (B)
ACOG The available evidence suggests
that MgSO4 given before
anticipated early preterm birth
reduces the risk of CP in
surviving infants. (A)
The Role Of Magnesium Sulfate (Mgso4) In Fetal Neuroprotection.Bachnas MA. THE JOURNAL OF MATERNAL-FETAL &
NEONATAL MEDICINE;2019
When and how to give
Intravenously with a 4 g loading dose
(slowly over 20–30 min) and 1 g per hour
maintenance dose via IV route for 12 h
could be given, and if delivery should not
proceed ,that initial dose continued by
maintenance dose could be administered for
only 12 h. (A)
Physicians electing to use antenatal
magnesium for fetal neuroprotection should
develop specific guidelines regarding of
inclusion criteria, treatment regimens,
concurrent tocolysis, and monitoring. There
is no specific statement about when and how
are stated (C)
 ANTICONVULSANT/
MAGNESIUM SULFATE
Guidelines Patients eligibility
RANZCOG  In women at risk of early preterm
imminent birth, the use of antenatal
magnesium sulfate for
neuroprotection of the fetus is
recommended. (A)
 It is strongly recommended if the
gestational age is 30 weeks or less.
(B)
 When early preterm birth is planned
or definitely expected within 24 h.
The neuroprotection protocol should
be started and finished before. (the
benefit is expected for the birth
occurring at least 4 h after initial
dose). (A)
When and how to give
• Intravenously with a 4 g
loading dose (slowly over
20–30 min) and 1g per
hour maintenance dose
via IV route, without
immediate repeated
doses. Continue to
regimen until birth or for
24 h, whichever comes
first. (A)
• Repeat according to
expertise (C)
• Delivery should not be
delayed in very urgent
case. (B)
• No place for magnesium
as tocolytic. (A)
 ANTICONVULSANT/
MAGNESIUM SULFATE

Guidelines Patients eligibility When and how to give

SOGC For women with imminent preterm birth • For women with imminent preterm
( 31þ6 weeks), antenatal magnesium birth, antenatal magnesium
sulfate administration should be sulphate for fetal neuroprotection
considered for fetal neuroprotection. (A) should be administered as a 4g IV
loading dose, over 30 min,
followed by a 1g/hr maintenance
infusion until birth. (B)
• No evidence to repeat. (B)
• Delivery should not be delayed in
emergency case. (B)
• No place for magnesium as
tocolytic. (A)

SA Perinatal MgSO4 for fetal neuroprotection is • MgSO4 can be administered

Practice indicated for women at risk of preterm
Guidelines birth within 24 h or planned, who are at
least 24þ0 weeks of gestation an <30þ0
weeks of gestation.
intravenously by syringe pump or
infusion pump regimen
• Loading dose is 4 g over 20 min,
continued by maintenance dose of 1
g/h.
• For transferring women to a
tertiary center, intramuscular route
can be used as a maintenance dose.
■ MgSO4therapy was associated with a significantly lower incidence of recurrent seizures compared to women given
an alternative anticonvulsant—9.7 versus 23 percent
■ Importantly, the maternal death rate of 3.1 percent with MgSO4 was significantly lower
than that of 4.9 percent for the other regimens.
 ANTIHYPERTENSION

Onset Peak
Class Medicine Dose
(Min) (Min)

Hydralazi 10 –
Dilator arterial 60 5 -10 mgIV/ 15-30 min
ne 20

Calcium channel
Nifedipine 10 60 10 – 20 mg PO/ 30 min
blocker

20-40-80 mg IV/
α/β blocker Labetalol 5 60
10-20 min-300 mg

Sodium
Dilatator arteria/
nitroprussi 0,5 - 5 5 0, 2-5, 0 µg/ kg/ min
vena
de
 TIMING OF
DELIVERY IN
PREECLAMPSIA

Delivery is strongly advised at 37+0 wg or

in the presence of any of the followings :
 repeated episodes of severe hypertension
despite maintenance treatment with 3
classes of antihypertensive agents
 progressive thrombocytopenia
 progressively abnormal renal or liver
enzyme tests
 pulmonary edema
 abnormal neurological features, such as
severe intractable headache, repeated
visual scotomata, or convulsions; or
nonreassuring fetal status.

Neither the serum uric acid nor the level of

proteinuria should be used as an
indication for delivery
 TERMINATION
OF
PREGNANCY

Vaginal or C. Section
The mode of delivery should be determined after considering the
presentation of the fetus and the fetal condition, together with
successful induction of labour after assessment of the cervix

Both of them are possible for the availability

TERMINATION OF
PREGNANCY

 Vaginal
In the active phase, there are no
other complications, a full
awareness / minimal
neurological disorders
 C. Section
Impairment of consciousness,
uncooperative, complications,
vaginal will be more than 8
hours, there are obstetric
indications, fetal distress
TATALAKSANA
KONSERVATIF

 Dilakukan di fasilitas
kesehatan tersier dengan
pengawasan ketat pada
keadaan ibu dan janin
 Pertimbangkan dengan
peningkatan risiko maternal
dan fetal (solusio plasenta,
gagal ginjal akut, edema
pulmo, DIC dan kematian)
 Bila keadaan ibu
memburuk  Terminasi
kehamilan
 KORTIKOSTEROID

ACOG merekomendasikan terapi Kortikosteroid antenatal

untuk mempercepat kematangan paru janin untuk wanita
hamil yang terkena dengan preeklamsia berat antara 24 – 34
minggu
 KORTIKOSTEROID

 Untuk maturasi paru janin

– Rekomendasi menggunakan Betametason (lebih aman dan
proteksi untuk otak janin)
– Cochrane update : penggunaan Kortikosteroid pada usia
kehamilan 26-34 minggu, single course antenatal dengan
Bethametasone 12 mg, dua kali pemberian
– Standar pemberian Kortikosteroid, pada usia 24-34 minggu
kehamilan dengan Bethametason 12 mg im perhari dalam 2
kali pemberian / per-12 jam, atau Deksametason 6 mg iv
setiap 12 jam, persalinan setelah 24 jam pemberia terakhir
Kortikosteroid
 Penggunaan Kortikoteroid berulang berisiko terhadap berat bayi
lahir rendah dan peningkatan risiko Cerebral palsy
KORTIKOSTEROID

 Pada wanita dengan

HELLP Syndrome
– Terapi Kortikosteroid
standar untuk maturasi
paru janin
– Terapi Deksametason
dosis tinggi untuk ibu
– Terapi dengan dosis
berulang untuk
mengurangi morbiditas
maternal dan
mempercepat
penyembuhan
 KORTIKOSTEROID

 Evaluasi manfaat bagi ibu  hanya efek minor dengan

terapi Kortikosteroid standar
 Manfaat Kortikosteroid
– Mengurangi edema, menghambat aktivasi endotel dan
mengurangi disfungsi endotel, mencegah anemia
trombotik mikroangiopati dan menghambat produksi
sitokin inflamasi
– Peningkatan jumlah trombosit dalam 48 jam
 KORTIKOSTEROID

 Penggunaan Deksametason dosis tinggi (10 mg/12 jam)

– Meningkatkan jumlah Trombosit dengan cepat
– Hanya direkomendasi untuk intervensi jangka
pendek
– Masih kontroversial karena penelitian lain tidak
dapat membuktikan penggunaan Deksametason
dosis tinggi dapat menurunkan komplikasi maternal
 TERAPI PREECLAMPSIA SAAT INI

MASALAH UTAMA :
TERAPI DEFINITIF
1. TERBENTUR
TERMINASI KEHAMILAN PREMATURITAS
(LAHIRKAN PLASENTA) 2. DATANG SUDAH
TERLANJUR DALAM
TERAPI SIMTOMATIK KOMPLIKASI
BERAT: EKLAMSIA,
• OKSIGENASI DAN HIDRASI CAIRAN TERUKUR HELLP SYNDROME,
• ANTI KEJANG OEDEMA
• ANTI HIPERTENSI PULMONUM,
GAGAL GINJAL

MASALAH UTAMA:
1. TIDAK MENGHAMBAT PROGRES PENYAKIT.
2. TIDAK BISA MEMPERBAIKI KOMPLIKASI YANG SUDAH TERJADI
 KITA MEMBUTUHKAN TERAPI BARU
YANG DAPAT MENCEGAH TERJADINYA
PENYAKIT, MENGHAMBAT
PROGRESNYA, ATAU BAHKAN
MENGOBATINYA SECARA DEFINITIF
 PREEKLAMPSIA

Peningkatan sFlt-1 dalam sirkulasi maternal

preeklampsia berhubungan erat dengan
berbagai manifestasi klinis pada
preeklampsia, antara lain peningkatan
tekanan darah & proteinuria
 TERAPI PREEKLAMSIA
BARU

sFlt-1 sebagai target gen terapi preeklampsia

melemahkan dominasi atau menghambat efek sFlt1

1. Pemberian protein rekombinan pro angiogenik – VEGF,
PlGF, peptides
2. Neutralizing Antibody melawan sFlt-1
3. Membuang sFlt-1 melalui metode extracorporeal
4. Chemical screening untuk molekul mikro atau siRNA yang
dapat memblok produksi sFlt-1
5. Plasmapharesis untuk membuang sFlt1
 PREEKLAMPSIA

TERAPI DENGAN
INJEKSI VEGF
 TERAPI VEGF
RECOMBINAN 121

• VEGF eksogen, proangiogenik polipeptida difusible serupa

VEGF asli/ endogen
• Bekerja dengan cara mengikat sFlt-1
• VEGF menekan T dengan cara merangsang endothel untuk
merilis NO dan prostaksiklin

• Terbukti baik untuk memperbaiki angiogenesis dan

vaskulogenesis
• Pada penelitian hewan coba tikus (inj. VEGF 125 ng/ kg berat
badan pada hari ke 8 -18 ) : ↓ tensi (61 %), memperbaiki
disfungsi endotel, ↓ tromboksan, ↓ IUGR, ↓ gagal ginjal, ↓
angiotensin tipe 1, ↓ hipoksia plasenta, memperbaiki sel
trphoblas yang rusak, menghambat sirkulasi sFlt-1 dalam darah.
 PLASMAPHERESIS

MEMISAHKAN ANTARA SEL DARAH DAN

PLASMA  PENGGANTIAN PLASMA YANG
TIDAK NORMAL (sFlt-1) DENGAN PLASMA
DONOR NORMAL

PROSEDUR INI DULUNYA DIKERJAKAN PADA

ITP, GBS DAN PENYAKIT IMUNOLOGIS LAIN

UNTUK PREEKLAMSIA TIDAK DISUBSTITUSI

DENGAN PLASMA DONOR MELAINKAN
DILAKUKAN AFARESIS DENGAN DEKSTRAN
SULFAT SELULOSA
Thank You