YUDIANTO BUDI SAROYO Diagnosis and Management of Pre-eclampsia in Pregnancy PDUI 2015 Final 4 s2

7/21/2019 YUDIANTO BUDI SAROYO Diagnosis and Management of Pre-eclampsia in Pregnancy PDUI 2015 Final 4 s2

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Staf Fetomaternal, Departemen Obstetri & Ginekologi FKUI/RSUPN

Cipto Manukusumo

Pelatih Basic Surgical Skill

POGI, tahun 2004‐

sekarang.

Fasilitator Advanced

Labour And

Risk

Management (ALARM)

POGI, tahun

2005‐

sekarang

Pelatih/Advanved Trainer

Jaringan

Nasiona

Pelatihan

Klinik‐Kesehatan

Reproduksi, tahun 2005‐

sekarang.

Pelatih

Resusitasi Neonatus Perinasia,

tahun 2004‐

sekarang.

Anggota

PokJa HIV/AIDS &

Pelatih

PMTCT

Kementerian Kesehatan

Republik Indonesia,

tahun 2007‐

sekarang.

Peserta

International Course

Sexual Reproductive

Health and

Right, Swedia, Pebruari

2009

Tujuan Pembicaraan

• Epidemiologi ‐ Latar Belakang

• Definisi

• Fisiologi Implantasi Plasenta

• Beberapa teori tentang Pre‐eklampsia

• Tatalaksana

• Pencegahan

• Kesimpulan

• Tera

Tujuan Pembicaraan


• Definisi



• Tatalaksana

• Pencegahan

• Kesimpulan

• Tera



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Goal 4: Menurunkan angka kematian balita

• Target 4a: Menurunkan 2/3 angka kematian balita.

Goal 5: Meningkatkan kesehatan maternal

• Target 5a: Menurunkan ¾ angka kematian maternal.

• Target 5b: Akses universal kesehatan reproduksi pada tahun 2015.

Goal 6: Memberantas penyakit HIV/AIDS, malaria dan

penyakit lainnya.

• Target 6a: Menghentikan dan mengurangi penyebaran HIV/AIDS

• Target 6b: Akses universal dan Pengobatan bagi seluruh penderita HIV/AIDS

• Target 6c: Menghentikan dan mengurangi insidens malaria.

Perdarahan

30%

Pre/Eklampsia

25%

Infeksi

12%

Abortus

5%

P. lama/macet

5%

Emboli obst

3%

Kompl masa

puerpureum

8%

Lain‐lain

12%

Prakiraan Waktu menuju Kematian untuk

Kasus Kegawatdaruratan Obstetri

Penyebab Waktu

Perdarahan Postpartum 2 jam

Perdarahan Antepartum 12 jam

Ruptur Uteri 1 hari

Eklampsia/PEB 2 hari

Persalinan Macet 3 hari

Infeksi 6 hari

Briley A, Bewley S. Management of obstetric hemorrhage: obstetric management. In: Briley A, Bewley S, editors. The Obstetric Hematology Manual.

Cambridge: Cambridge University Press; 2010. p. 151 ‐58.

Jangka Pendek:

HELLP,

CVD

Edema pulmonum,

Eklamsia

Jangka Panjang:

Gagal Ginjal Kronik,

Peny. Kardio Vaskular,

DM tipe 2

Anak:

Cerebral Palsy

DM tipe 2

Penyakit Kardio Vaskular

Obesitas

PCO

Teratozoospermia

Hypertension 2007;49(5):1056-62, J Clin Endocrinol Metab 2006;91(4):1233‐8



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Tujuan Pembicaraan


• Definisi



• Tatalaksana

• Pencegahan• Kesimpulan

• Tera

The revised ISSHP definition preeclampsia

(2014)

Hypertension developing after 20 weeks gestation and the

coexistence of one or more of the following new onset conditions:

1. Proteinuria

2 . O the r maternal organ dysfunction:

• Renal insufficiency (creatinine >90 umol/L)

• Liver involvement (elevated transaminases and/or severe right upper

quadrant or epigastric pain)

• Neurological complications

• Haematological complications

3. Uteroplacental dysfunction

• Fetal growth restriction

The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised

statement from the ISSHP. Pregnancy Hypertension: An International Journal of Women’s Cardiovascular

Health 4 (2014) 97–104

• Considered severely elevated: >160

mmHg systolic or >110 mmHg diastolic.

• Not to rely on a single reading,

appropriate‐sized cuff

• In the case of severely elevated BP not to wait for ‘‘6 h apart’’, but in 15‐30 m

• Suggest mercury sphygmomanometry or sphygmomanometry using a liquid crystal

device. If an automated device is to be

used then it should have been validated

for use in pregnancy.

Andrea L. Tranquilli, Mark A. Brown, Gerda G. Zeeman, Gustaaf Dekker, Baha M. Sibai. The definition

of severe and early‐onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP)

• Does not predict clinical outcome

• A spot urine protein/creatinine ratio > 30 mg/mmol

• There is no clear consensus on the amount of proteinuria to

be considered ‘severe’ (between >3 and 5 g/l)• NOT CONSIDER PROTEINURIA FOR DEFINING SEVERE

PREECLAMPSIA

Andrea L. Tranquilli, Mark A. Brown, Gerda G. Zeeman, Gustaaf Dekker, Baha M. Sibai. The definition

of severe and early‐onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP)



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• Disease of theories

• Insiden: 16.3%, MM: 1.9%, MP: 9.9%

• Th/ Definitif: Lahirkan dengan segala risiko

• Pencegahan: upaya terbaik, hasil tidak bermakna???????

Buku Tahunan 1993‐1994, BMJ 2007;335(7627):974,

Hypertension 2007;49(5):1056-62, J Clin EndocrinolMetab 2006;91(4):1233‐8

Hipertensibukan

penyakit tapimerupakanreaksi tubuh

Hipertensi terjadisebagai

mekanismekompensasi

penuhi kebutuhan

Implantasiyang tak

sempurna

Tujuan Pembicaraan


• Definisi



• Tatalaksana

• Pencegahan

• Kesimpulan

• Tera



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Tujuan Pembicaraan


• Definisi



• Tatalaksana

• Pencegahan

• Kesimpulan

• Tera

Failure SMC modification

Syncytial knot: aptototic sincytrophoblast

ROS dan RNS berperan penting pd PEE

– Scr langsung induksi disfungsi endothelial

– Induksi hipertensi dan proteinuria melalui:

• RAS

• inflammasi

• Insulin resistan

• Pro – anti angiogenic

• menurunkan NO dg meningkatkan

ADMA dan menurunkan HO‐1

Aliran drh: tonik O2‐ hipertensi

Poiseuille’s+Bernoulli’s

Diameter : ↑ 4 – 6 X

Exp.Physiol 1997; 82;377 -87

• Kantungelastis

• Bertahananrendah

•Arus tinggi

• Bebasregulasi neurovascular

Debris ke sirkulasi maternal sitokin disfungsi endotel

Prooxidant – antioxidant alance

Perkembangan Pre‐eklampsia

Ramma W, Ahmed A. Is inflammation the cause of pre‐eclampsia? Biochem Soc Trans. 2011 Dec;39(6):1619‐27.

Skema sekuen kejadian sepanjang kehamilan sampai timbul gejala klinis pre‐eklampsia. EC,

endothelial cell; HO‐1, haem oxygenase 1; TGF‐β , transforming growth factor β.

Two‐stage model of development of preeclampsia

CHRISTOPHER W.G. REDMAN, IAN L. SARGENT AND ROBERT N. TAYLOR. Immunology of Normal Pregnancy and Preeclampsia. Chesley’s Hypertensive Disorder in Pregnancy



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CHRISTOPHER W.G. REDMAN, IAN L. SARGENT AND ROBERT N. TAYLOR. Immunology of Normal Pregnancy

and Preeclampsia. Chesley’s Hypertensive Disorder in Pregnancy

Four‐stage model of development of preeclampsia Possible pathophysiological processes in pre‐eclampsia

AV=anchoring villus. COE=coelomic cavity. CY=cytotrophoblast. DB=decidua basalis. DC=decidua capsularis. DP=decidua parietalis.

EN=endothelium. ET=extravillous trophoblast. FB=fetal blood vessel. FV=fl oating villus. GL=gland. IS=intervillous space. JZ=junctional

zone myometrium. MB=maternal blood, leaving the intervillous space with various components such as antiangiogenic factors.

MV=maternal vein. SA=spiral artery. SM=smooth muscle. ST=stroma. SY=syncytiotrophoblast. TM=tunica media. UC=uterine cavity. sFlt‐

1=soluble form of the vascular endothelial growth factor receptor. Centre panel of fi gure adapted from Karumanchi et al,18 with

permission from Elsevier.

Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre‐eclampsia. Lancet. 2010 Aug 21;376(9741):631‐44.

The pathophysiological processes

involved in pre‐eclampsia

Urato AC, Norwitz ER. A guide towards pre‐pregnancy management of defective implantation and placentation. Best Pract Res Clin Obstet Gynaecol. 2011 Jun;25(3):367‐87.

AT1‐AA, angiotensin II receptor 1 autoantibodies; HELLP, hemolysis, elevated liver enzymes, and

low platelets; PlGF, placental growth factor; sFlt‐1, soluble Fms‐like tyrosine kinase‐1; VEGF,

vascular endothelial growth factor.

Faktor‐faktor Risiko dan Patogenesis

Preeklampsia.

Genetik, faktor lingkungan dan faktor imun menyebabkan plasentasi yang dangkal dan perfusi uteroplasenta selama akhir kehamilan dan memicu pelepasan faktor –faktor yang mempengaruhi pembuluh darah sistemik dan menyebabkan vasokonstriksi umum, resistensi pembuluh darah meningkat dan pre‐eklampsia. Faktor‐faktor bioaktif tersebut bisa melukai ginjal menyebabkan volume plasma meningkat dan hipertensi berat, serta endotheliosis glomerulus dan proteinuria. Dapat pula meningkatkan permeabilitas pembuluh darah otak dan menyebabkan edema sehingga eklampsia..

Reslan OM, Khalil RA. Molecular and vascular targets in the pathogenesis and management of the hypertension associated with preeclampsia. Cardiovasc Hematol Agents Med Chem. 2010 Oct 1;8(4):204‐26.



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Anne Cathrine Staff, et al. Redefining Preeclampsia Using Placenta ‐Derived Biomarkers. Hypertension. 2013;61:932‐942 Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009 Jun;24:147‐58.

Summary of the pathogenesis of preeclampsia

Immune factors (such as AT1‐AA), oxidative stress, NK cell

abnormalities, and other factors may cause placental dysfunction, which in turn leads

to the release of anti‐

angiogenic factors (such as sFlt1

and sEng) and other

inflammatory mediators to induce hypertension,

proteinuria, and other complications of preeclampsia.

Genetik

Immunologik

Nutrisi

Infeksi

Perubahan pada angiogenesis

Fetoplacental

Stress

Oxidative

Kegagalan

Invasi

Trophoblast

Lain2:VEGF

TNF

dll

Disfungsi Endothel

Hypertensi & Proteinuria

PREEKLAMPSIA

Etiologic Factors

Pathophysiology

Clinical Manifestation

Overlapping role of hypertension, capillary leak, maternal

symptoms, and fibrinolysis/hemolysis in the spectrum of

atypical preeclampsia

Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia‐eclampsia. Am J Obstet Gynecol. 2009 May;200(5):481 e1‐7.

/ /



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PREECLAMPSIA

Tujuan Pembicaraan


• Definisi



• Tatalaksana

• Pencegahan

• Kesimpulan

• Tera

Tujuan Pembicaraan


• Definisi



• Tatalaksana – Konservatif

– Eklampsia

– Antihipertensi

– Balans cairan

• FIRST, delivery is always appropriate therapy for the mother

but not be so for the fetus

• SECOND, the signs and symptoms of preeclampsia are not

pathogenetically important (lowering blood pressure do not

alleviate the important pathophysiologic changes

• THIRD, the pathogenic changes or preeclampsia are present

long before clinical criteria for diagnosis are evident

F. Gary Cunningham. Hypertensive disorders. Williams Obstetrics ed 24th

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Antepartum management options for women with pre‐

eclampsia by gestational age at diagnosis

NICU=neonatal intensive care unit. *As defi ned locally (usually between 23 weeks’ [+0 days] and 24 weeks’ [+6 days] gestation). †Unpublised

data from PIERS.86 ‡Chance of living to discharge from a NICU without major morbidity (≥grade 3 intraventricular haemorrhage, stage 3 or 4

retinopathy of prematurity, necrotising enterocolitis, and chronic lung disease).


Antepartum management options for women with pre‐

eclampsia by gestational age at diagnosis

NICU=neonatal intensive care unit. *As defi ned locally (usually between 23 weeks’ [+0 days] and 24 weeks’ [+6 days] gestation). †Unpublised

data from PIERS.86 ‡Chance of living to discharge from a NICU without major morbidity (≥grade 3 intraventricular haemorrhage, stage 3 or 4

retinopathy of prematurity, necrotising enterocolitis, and chronic lung disease).

Suggested antepartum management options for women

with pre‐eclampsia at any stage of diagnosis

Optional assessment and surveillance

• On admission, on day of delivery, and additional

testing as indicated by changes in clinical state.

Maternal

• Blood: haemoglobin, platelet count, creatinine,

uric acid, AST or ALT, further testing if indicated

Fetal

• CTG, ultrasound, AFI, umbilical artery Doppler


SEIZURE PROPHYLAXIS AND TREATMENT

• In the Magpie study, 10,000 preeclamptic women were randomized

to receive magnesium sulfate or placebo.

• Magnesium sulfate clearly reduced the risk of eclampsia in this trial,

and it was shown to be superior to other prophylactic medications,

including phenytoin, and diazepam.

RCT of MgSO4 prophylaxis with placebo or active drug in women with gestational hypertension

JAMES M. ALEXANDER AND F. GARY CUNNINGHAM. Clinical Management. . Chesley’s Hypertensive

Disorder in Pregnancy

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Randomized comparative trials of Magnesium Sulfate

with Another Anticonvulsant to Prevent Recurrent

Eclamptic Convulsions



• In women with normal renal function, the half ‐time for excretion is

about 4 hours.

• Because excretion depends on delivery of a filtered load of

magnesium that exceeds the Tmax, the half ‐time of excretion is

prolonged in women with a decreased GFR

Magnesium slows or blocks neuromuscular and cardiac conducting

system transmission, decreases smooth muscle contractility, and

depresses central nervous system irritability




MgSO4

• Regimen: MgSO4 4 g IV loading dose over 15–20 min, followed by an infusion of 1 g/h; recurrent seizure(s) treated with additional 2–4 g IV loading dose(s); clinical

monitoring by measurement of urinary output, respiratory rate, and tendon refl exes.

Eclampsia prophylaxis

• Yes; for severe pre‐eclampsia during initial stabilisation and peripartum (delivery +24 h)

Eclampsia treatment

• Yes

• Inhibition of uterine contractility is magnesium dose

dependent

• Serum levels of at least 8‐10 mEq/L are necessary to inhibit

uterine contractions (Watt‐Morse, 1995)



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100 200

Normotensive

Poorly controlled

hypertensive

Mean Arterial Pressure (MAP)

Cerebral Blood Flow

Risk of

hypertensive

encephalopathy

Risk of

ischemia

50 150 250

Loss of Autoregulation

Adapted with permission from Varon J, Marik PE. Chest. 2000;118:214‐227.

JASON G. UMANS, EDGARDO J. ABALOS AND F. GARY CUNNINGHAM. Antihypertensive treatment. Chesley’sHypertensive Disorder in Pregnancy

Randomized Placebo‐Controlled Trials of Antihypertensive Therapy for Early

Mild Hypertension During Pregnancy

JASON G. UMANS, EDGARDO J. ABALOS AND F. GARY CUNNINGHAM. Antihypertensive treatment. Chesley’s Hypertensive Disorder in Pregnancy

DRUGS FOR TREATMENT OF SEVERE HYPERTENSION IN PREGNANCY

Drug Dose Onset Duration Adverse Effects

Hydralazine 5–10 mg IV q 20 min 10–20 min 3–6 h Ta chy ca rd ia , headache, flushing,

aggravation of angina

Labetalol 20–40 mg IV q 10 min 1

mg/kg as needed

10–20 min 3–6 h Scalp tingling, vomiting, heart block

Nifedipine 10–20 mg PO q 20–30 min 10–15 min 4–5 h Headache, tachycardia, synergistic interaction with magnesium sulfate

Nicardipine 5–15 mg/h IV 5–10 min 1–4 h Ta chy ca rd ia , headache, phlebitis

Sodium

nitroprusside

0.25–5 μg/kg/min IV Immediate 1–2 m in N aus ea, vomiting, muscle twitching,

thiocyanate and cyanide intoxication

Nitroglycerin 5–100 μg/min IV 2–5 min 3–5 m in H ea da ch e, methemoglobinemia,

tachyphylaxis



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Fluid Management

Rapid fluid infusion a significant increase in alveolar‐

arterial oxygen difference (AaDO,) and shunt fraction (Qs/Qt)

Vasodilator therapy alone appears to improve tissue

oxygenation without affecting Qs/Qt

F. Gary Cunningham. Hypertensive disorders. Williams Obstetrics ed 24th

• Oliguria (<15 mL/h) is common in preeclampsia, particularly

postpartum.

• In the absence of pre‐existing renal disease or a rising

creatinine, oliguria should be tolerated over hours, to avoid

volume‐dependent pulmonary oedema

Laura A. Magee, Anouk Pels, Michael Helewa, Evelyne Rey, Peter von Dadelszen, On behalf of the

Canadian Hypertensive Disorders of Pregnancy (HDP) Working Group 1. Diagnosis, evaluation, and

management of the hypertensive disorders of pregnancy




Plasma volume expansion

• No; because of risks of maternal mortality associated with pulmonary oedema, in women

with severe pre‐eclampsia infusion of sodium‐containing fluids might need to be restricted and balanced against urine output over 4 h or more and creatinine concentrations

Thromboprophylaxis

• Yes; if on bed rest for 4 days or more

Tujuan Pembicaraan


• Definisi



• Tatalaksana

• Pencegahan

• Kesimpulan

• Tera





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/ /

Upaya pencegahan

• Pra konsepsi optimalkan status nutrisi – Multivitamin dan mineral, protein dan mix karbohidrat

– Bereskan infeksi: periodontitis, UTI, cervico vaginitis

– Upayakan berat badan ideal

– Olah raga teratur

• Saat hamil – Pertahankan upaya pra konsepsi

Kontrasepsi

KOK KIK KOP KIP Implan

Pil

Kondar AKDR

AKDR‐

LNG TubektomiRiwayat TD

tinggi selama

kehamilan

(sekarang TD

normal)

2 2 1 1 1 ‐ 1 1 A

Sistolik 140–

159 atau

diastolik 90–99

3 3 1 2 1 ‐ 1 1 C

Sistolik ≥ 160

or diastolik ≥

100

4 4 2 3 2 ‐ 1 2 S

KOK= Kontrasepsi oral kombinasi; KIK= Kontrasepsi injeksi kombinasi; KOP= Kontrasepsi oral

progestin; KIP= Kontrasepsi injeksi progestin; Kondar =kontrasepsi darurat; AKDR= alat

kontrasepsi dalam rahim; AKDR‐LNG= alat kontrasepsi dalam rahim Levonorgestrel.

Kate J Kerber, Joseph E de Graft ‐ Johnson, Zulfi qar A Bhutta, Pius Okong, Ann Starrs, Joy E Lawn. Continuum of care for maternal, newborn, and child health: from slogan to service delivery. Lancet 2007; 370: 1358–69

Kate J Kerber,

Joseph

E de

Graft

‐ Johnson,

Zulfi

qar

A

Bhutta,

Pius

Okong,

Ann

Starrs,

Joy

E Lawn.

Continuum

of

care

for

maternal, newborn, and child health: from slogan to service delivery. Lancet 2007; 370: 1358–69

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Kesimpulan

• Preeklampsia masih merupakan salah satu

penyebab kematian maternal.

• Pengertian mendalam tentang patofisiologi

preeklampsia akan mengurangi dampak

preeklampsia.

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YUDIANTO BUDI SAROYO Diagnosis and Management of Pre-eclampsia in Pregnancy PDUI 2015 Final 4 s2

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