MANAGEMENT OF PREECLAMPSIA BY DR SHASHWAT JANI

MANAGEMENT OF PREECLAMPSIA BY DR SHASHWAT JANI

1. Dr. Shashwat Jani.
M. S. ( Obs – Gyn ), F.I.A.O.G.
Diploma in Advance Laparoscopy.
Consultant Assistant Professor,
Smt. N.H.L. Municipal Medical College.
Sheth V. S. General Hospital , Ahmedabad.
Mobile : [phone].
E-mail : [email protected]

2. Introduction
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Dr Shashwat Jani.
99099 44160.
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• Hypertensive disorders are common
complications of pregnancy, affecting 8% to 10% of
all gestations.
• Approximately 1/3 of hypertensive disorders in
pregnancy (HDP) are due to chronic hypertension
and 2/3 are due to gestational hypertension–
preeclampsia.
• The spectrum of the disease ranges from
mildly elevated blood pressures with minimal
clinical significance to severe hypertension and
multi organ dysfunction.

3. Among top 3 causes
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Hypertensive disorders of pregnancy (HDP) are one of the major causes of maternal
morbidity and mortality leading to 10-15% of maternal deaths.

4. HTN disorders complicates
8-10% of all pregnancies
Pre-eclampsia complicates
3-9% of pregnancies in
developed countries

5. Nothing has changed…
• The first description of Preeclampsia was given by
Hippocrates, a father of modern medicine (460-377 BC), a
son of Heraclides from the island of Kos .
• Even after more than two millennia since the first
descriptions, the syndrome of preeclampsia/ eclampsia
(PE/E) has remained a multi-system disorder of unknown
etiology.

• The diagnosis is based on a clinical picture and
laboratory analysis;
BUT, an efficient prevention and screening are still missing,
The therapy is ONLY symptomatic,
While giving birth STILL REMAINS the only causal therapy.
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99099 44160.
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6. ALERT
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10. Major changes of the new
classification are as follows:
(1) HDP is defined as hypertension in pregnancy.
(2) Eclampsia was removed from the major classification.
(3) Chronic hypertension was added to the major classification.
(4) If pregnant women with new onset of hypertension have either
maternal organ dysfunction or uteroplacental dysfunction, they
should be diagnosed with preeclampsia, even in the absence of
proteinuria.
(5) The severity classification should be ‘severe’ when hypertension is
severe, or when hypertension is mild but there is maternal organ
dysfunction or uterine placental dysfunction. The term ‘mild’ was
excluded from the criteria of HDP because it can be misinterpreted to
mean ‘not at high risk’.
(6) The definition of ‘early onset type’ is that which appears earlier
than 34 weeks gestation, in accordance with international standards.
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PIH

11. The New Vs. the Old classifications
• Pre-eclampsia does not require the presence of
proteinuria for Dx.
• Pre-eclampsia may be diagnosed if HTN +
– Thrombocytopenia (PLTs<100k)
– Liver injury (ALT/AST > x2 UNL)
– Renal dysfunction (SCr>1.1 or x2 from baseline*)
– Pulmonary edema
– New onset cerebral or visual disturbances
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99099 44160.
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12. Classification of Hypertensive
Disorders of Pregnancy
Hypertension
in pregnancy
Chronic
hypertension
Gestational
hypertension
Preeclampsia
Preeclampsia
superimposed
on chronic
hypertension
Jim et al., Cardiology Review 2010;18: 178–189

13. Updated Classification of
Hypertensive disorders of pregnancy
1. Preeclampsia (PE) (BP elevation after 20 weeks of
gestation with proteinuria OR any of the severe
features of preeclampsia)
2. Chronic hypertension (CHTN, of any cause that
predates pregnancy)
3. Chronic hypertension with superimposed
preeclampsia (chronic hypertension in association with
preeclampsia)
4. Gestational hypertension (GH: BP elevation >20
weeks of gestation in the absence of proteinuria or any
of the severe features of preeclampsia.
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99099 44160.
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14. As per National High Blood Pressure
Education Program (NHBPEP)
Normal or acceptable BP SBP ≤140 & DBP ≤ 90 mmHg

Mild hypertension SBP 140 - 159 or DBP 90 -109
mmHg

Severe hypertension SBP ≥ 160 or DBP ≥110
mmHg

Brown CM et al. Drugs. 2014 March ; 74(3): 283–296.

15. Severe Preeclampsia
•Severe hypertension: Systolic ≥ 160 mm Hg and
/or diastolic ≥ 110 mm Hg
•Severe proteinuria: >5 g/24 h
•Severity symptoms: Right upper quadrant or
epigastric pain, headache, blurred vision
•Abnormal lab: Thrombocytopenia, Elevated liver
enzymes, Raised creatinine
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99099 44160.
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16. Abnormality Mild Severe
Headache × ✓
Visual disturbances × ✓
Eclampsia × ✓
Upper abdominal pain × ✓
Pulmonary edema × ✓
Proteinuria Trace to 1+ Persistent 2+ or more
Oligouria × ✓
Serum creatinine Normal Elevated
Thrombocytopenia × ✓
Hyperbilirubinemia × ✓
Liver enzyme elevation Minimal Marked
Fetal growth retardation × ✓
But, BP not always a dependable indicator of severity
Mild Vs. Severe Preeclampsia

17. Which Urine Test ?
Dipstick
Semi-quantitative, screening only
Affected by urine concentration, highly variable
Detection of urine albumin > 300 mg/day
1+ approximates albumin excretion of 30 mg/day)
Urine protein/creatinine ratio
All proteins, not just albumin (myeloma/CIN)
Urine albumin-to-creatinine ratio (UACR)
Quantifies urine albumin
Steps toward standardization currently in progress
Standard for public health, clinical care, and research
24hr collection (or other timed)
Gold standard/cumbersome
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99099 44160.
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18. Etiopathogenesis
Still not clear…
But Possibilities are…
Defective trophoblastic invasion.
Imbalance between angiogenic and anti-
angiogenic growth factors (VEGF, PEGF, sFLT-1)
Genetic predisposition
Aberrant maternal immune response to
gestation
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99099 44160.
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19. Prediction Of PE
•Why prediction is important?
•The ideal screening test
•Methods
I. Preconception factors
II. Pregnancy-Related Factors
1. Risk factors
2. Markers

20. Why prediction is important:

1.The risk for recurrent PE can be as
high as 35% (Barton& Sibai, 2008).
2.PE is associated with substantial
maternal & perinatal complications

21. The ideal Screening test:
Simple
Noninvasive
Rapid
Inexpensive
Easy to perform early in
pregnancy
Highly sensitive & predictive.

22. 1.Preconception factors

1
st
step in the management of
a woman with a history of PE is to
conduct a detailed evaluation of
potential risk factors (Barton& Sibai, 2008).

23. Preconceptional Risk Factors
Rates of preeclampsia depend on: severity of
underlying complications & combinations of risk factors.

Risk % Risk factors
15-40 Chronic hypertension/renal disease
10-35 Pre gestational DM
10-20 Connective tissue disease (lupus, rheumatoid arthritis)
10-40 Thrombophilia (acquired or congenital)
10-15 Obesity/insulin resistance
10-20 Age older than 40 y
10-35 Limited sperm exposure
10-15 Family history of preeclampsia/ cardiovascular disease
1.5 fold Woman born as SFGA
2-3 fold Adverse outcome in a previous pregnancy: IUGR, ab placentae, IUFD

24. II. Pregnancy-Related Factors

 Risk factors: Magnitude of risk depends on the number of factors
Hydrops/hydropic degeneration of the placenta
Multifetal gestation
Unexplained FGR
Gestational hypertension
UTI
Periodontal infection
 Markers
Biophysical
Biochemical

25. Markers
Many
Based on: pathophysiological abnormalities

26. • SCREENING TESTS FOR PE (WHO, 2004)
I. Placental perfusion & vascular resistance dysfunction
Mean arterial blood pressure
Roll over test
Doppler ultrasound
Isometric exercise test
Intravenous infusion of angiotensin II
Platelet angiotensin II binding
Platelet calcium response to arginine vasopressin
Renin
24-hour ambulatory blood pressure monitoring
II. Fetoplacental unit dysfunction
Human chorionic gonadotropin
Alpha fetoprotein
Estriol
Inhibin A
Pregnancy-associated plasma protein A
Activin A
Corticotropin release hormone

27. III. Renal dysfunction
Serum uric acid
Microalbuminuria
Urinary calcium excretion
Urinary kallikrein
Microtransferrinuria
N-acetyl- glucosarninidase


Platelet count
Platelet activation and endothelial cell
adhesion molecules
Prostacyclin
Cytokines
Isoprostanes,
Antiphospholipid antibodies,
Placenta growth factor
Hematocrit
Antithrombin Ill
Calcium
Transferrin
Atrial natriuretic peptide
Fibronectin
Endothelin
Thromboxane
Homocysteine
Serum lipids Insulin resistance
Plasminogen activator inhibitor
Leptin
Total proteins
Magnesium
Ferritin
Haptoglobin
microglobulin
Genetic markers
IV. Endothelial& oxidant stress dysfunction

28. I. Biophysical
Mean arterial pressure

•(2D BP+S BP)/3
•Better predictor of PE than S & D BP
(BMJ 200817;336:111; Meta-analysis of 34 RCT)

•BP remains the cornerstone of early diagnosis although it
has limitations:
Measurement errors associated with sphygmomanometer
Effect of maternal posture on BP in pregnant women.

29. •Repeated routine urinalysis

Throughout pregnancy NOT useful for
predicting PE
(JAMA 2003: 12;289(10):1220)

30. Uterine artery Doppler ultrasound
•}impaired trophoblastic invasion of the spiral arteries:
reduction in uteroplacental blood flow}
•High pulsatility index and/or Notch in 1
st
& 2
nd
trimesters:
poor predictor of PE(Papgeorghiou & Leslie, 2007)

Uterine artery Doppler plus biochemical markers
•Promising results
•BUT , Current data do not support this combination for
routine screening for PE (Barton& Sibai, 2008).

31. II. Biochemical Markers

Angiogenic factors before & after the onset
of PE
(Barton& Sibai, 2008).
Serum placental growth factor: Reduced
Soluble fms-like tyrosine kinase: Elevated
Endoglin : Elevated

32. But Remember…
•BP remains the cornerstone of early diagnosis
.
•Markers
Reliability is inconsistent
Many suffer from poor specificity & predictive
values.
None provided a cutoff value that could be
clinically useful for the prediction of PE
(Widmer et al, 2007).

34. Early Vs. Late Preeclampsia
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99099 44160.
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35. Treatment Objectives
To stabilize the hypertension and to prevent
severe pre-eclampsia.
To prevent the complications.
To prevent eclampsia.
Delivery a healthy baby in optimal time.
Restoration of the health of the mother in
Puerperium.
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99099 44160.
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36. Prevention
•Do’s
-- Smoking cessation
– Low dose ASA before 16GW
(high risk populations)
– Moderate exercise
• Don’t s:
– Calcium supplement
– Anti-oxidants
– Low salt diet
– Bed rest
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99099 44160.
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37. Pre-eclampsia without severe
features
> 37 weeks gestation: deliver
< 37 weeks gestation: expectant management until
term or maternal/fetal indication for delivery
– Bedrest no longer “suggested”
– Serial maternal assessment (BP, symptoms, labs,
weight gain)
– Serial fetal assessment (NST/BPP, fetal kick count,
serial Us for AFI and growth)
– Oral antihypertensives
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99099 44160.
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38. Severe Preeclampsia
>34 weeks: deliver
33-34 weeks: steroids and deliver after 48 hours if
maternal/fetal status allows
22-32 weeks: antihypertensive meds(oral/IV), steroids,
extensive counseling, close surveillance deliver for
maternal/fetal indications or 34 weeks gestation
< 22 weeks : expectant mgmt not recommended
Start MgSO4 upon diagnosis irrespective of Gest. Age .
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Dr Shashwat Jani.
99099 44160.
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39. Factors affecting the efficacy
of AHT drug

•Familiarity and experience with the drug
•Knowledge of doses and interactions with the
drug
•Fetal and maternal adverse effects
•Effect on utero-placental blood flow
•Onset of action
•Duration of action
•Ease of administration
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Dr Shashwat Jani.
99099 44160.
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40. Antihypertensive therapy for
Preeclampsia
•Antihypertensive therapy should be started with
systolic BP =/> 150 and /or diastolic BP =/> 100
mm Hg.
•Aim of therapy should be to lower BP to < 140
mmHg systolic and < 90 mmHg diastolic.
•Oral antihypertensive agents to be used are:
alpha methyldopa, labetalol, and nifedipine.
The medical provider must be familiar with the
dose to be used, the expected onset of action, and
potential side effects of each of these medications.

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41. •Nifedipine should not be given sublingually.
•ACE inhibitors and angiotensin receptor
blockers are contraindicated during
pregnancy.
•Chronic hypertensive women already on
these medications should be switched to
safer antihypertensive during pregnancy
•Atenolol and Prazosin are not recommended.

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Dr Shashwat Jani.
99099 44160.
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42. Treatment of Mild Preeclampsia
Mode of
Action
Starting
Dose
Maximum
Dose
Contra-
indications
Breast
Feeding
Methyl Dopa
Centrally
acting 
agonist
250mg bd 1 gram tds Depression Yes
Labetolol
 + 
antagonist
100mg bd 600mg qid Asthma Yes
Nifedipine
SR
Ca channel
antagonist
10mg bd 40mg bd Yes
Hydralazine Vasodilator 25mg tds 75mg qid Yes
(Avoid Diuretics / ACE Inhibitors)

43. Labetolol – 1
st
Line Drug
•A salicylamide derivative, discovered by Dr.
L.H.C. Lunts & his colleagues .
•Antihypertensive drug (oral as well as i.v.)
•Combined both selective,
competitive α1-adrenergic blocking and
nonselective, competitive β-adrenergic blocking
activity

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99099 44160.
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44. Pharmacodynamics
LABETALOL
Selective α
1 receptor blockade
Vasodilatation
↓ Peripheral resistance
Nonselective ß
receptor blockade
Protects heart from
reflex sympathetic drive
↓ Blood pressure
Blood vessels Heart

45. Severe Preeclampsia
( Hypertensive Crisis )

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99099 44160.
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46. Remember :
•Lower BP promptly but slowly: AIM for BP <
150/100 mm Hg
•Loading Dose of MgSO4 is Recommended to
Prevent Eclampsia in all Severe Preeclampsia.
•No need of maintenance dose here. Pregnancy
can be safely continued after desired BP control.
•Expectant management is done at tertiary centre
only if there is no maternal organ involvement
there is no immediate danger to fetus to get time
to use steroids for fetal lung maturity.
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99099 44160.
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47. Timing Of Delivery
Gestational hypertension can be taken to term.
Mild preeclampsia should be delivered at 37 weeks.
Severe preeclampsia should be delivered after 34 weeks.
Eclampsia should be delivered once stabilized with MgSO4
at any weeks of gestation.
Corticosteroids are given for fetal lung maturity where
appropriate.
Intramuscular Dexamethasone 6 mg 6 hourly 4 doses or
12 mg 12 hourly 2 doses.
Cesarean section is done for Obstetric indications only.
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48. Method of delivery
•Induction of labor
•Cesarean section
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49. Indication of Induction Of Labour
• Aggravation of the preeclamptic features in spite of
medical treatment and/or appearance of newer
symptoms
• Hypertension persists in spite of medical treatment
with pregnancy reaching 37 weeks or more.
• Acute fulminating pre-eclampsia irrespective of the
period of gestation
• Tendency of pregnancy to overrun the expected
date.
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50. Indication Of C.S.
• When an urgent termination is indicated and
the cervix is unfavorable (unripe and closed).

• Severe pre-eclampsia with a tendency to
prolong the induction delivery interval.

• Associated complicating factors, such as
elderly primigravidae, contracted pelvis,
malpresentation, etc
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99099 44160.
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51. Crises in Pre-eclampsia
Eclampsia
HELLP syndrome
Pulmonary Oedema
Placental Abruption
Cerebral Haemorrhage
Cortical Blindness
DIC
Acute Renal Failure
Hepatic Rupture

52. Postnatal Mx.
Blood Pressure
•In women with pre-eclampsia who did not take
antihypertensive treatment and have given birth, measure
blood pressure:
at least four times a day
•while the woman is an inpatient
at least once between day 3 and day 5 after birth
•on alternate days until normal if blood pressure was abnormal
on days 3–5.
•Stop Methyldopa , if she is taking.
•Measure platelet count, transaminases and serum creatinine
48–72 hours after birth.
•Contraception.
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FEBRUARY 2018

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57. To determine whether oral
labetalol is associated with a
shorter time to blood
pressure control compared to
oral extended release
nifedipine for management of
persistent postpartum
hypertension

58. Conclusion:

Both labetalol and nifedipine were effective for control of
persistent postpartum hypertension.

However, labetalol achieved control significantly more often with
the starting dose and had fewer side effects
Results:

The time to achieve BP control was similar between labetalol and
nifedipine groups (37.6 hours versus 38.2 hours, p = 0.51).

No major side effects were observed

59. Labetalol as a first-
line drug for
hypertension in
pregnancy and
endorse its
superiority over
alpha-methyldopa

60. WHY NOT ALPHA-METHYLDOPA ?
Upon introduction, alpha-methyldopa takes 24 hours
for complete action.
Upon starting with a 250 mg dose, it needs to be taken
three times daily.
Patients commonly suffer from postural hypotension
due to alpha-receptor blockade.
Common side effects are constipation, galactorrhea,
postpartum depression and altered sleep pattern.
It also causes headache, which can be confused with
impending eclampsia.
Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

61. WHY NOT ALPHA-METHYLDOPA ?
Hematological manifestations include hemolysis
and thrombocytopenia on blood smear and false
positive Coomb’s test in 10% cases.
It causes falsely non-assuring fetal heart patterns
on electronic fetal monitoring.
Alpha-methyldopa accumulates in renal failure,
which can sometimes complicate pre-eclampsia
Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

62. Why Labetalol?
Free of the side effects mentioned for methyl-dopa
It results in good and sustained control of BP.
There is no tachycardia and BP is stabilized.
Labetalol has no effect on uteroplacental blood flow
Injectable form is available for hypertensive crisis
Indian Journal of Clinical Practice, Vol. 23, No. 10 March 2013

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