This is a multisystem disorder with implications for

both mother and fetus.

It is hypertension in pregnancy of two consecutive

blood pressure readings, spaced 6 hours apart, greater than 140/90mmHg and proteinuria of greater than 300mg in 24 hours. It only occurs after the 20th week of gestation (that is, after late 2nd or 3rd trimester), that is in a previously normotensive patient.

 The development of epileptiform convulsions in the

pregnant patient in association with a diagnosis of preeclampsia Seizures are usually grand-mal tonic clonic

 Usually asymptomatic but can manifest in severe

disease with:
Headache(especially frontal) Visual disturbance Epigastric or Right upper Quadrant(RUQ) pain

Nausea and Vomiting

Rapid Edema (especially face)

 Hypertension (rise of 15mmHg over booking blood

pressure) Proteinuria(>300 mg in 24 hours) Facial edema Epigastric/RUQ tenderness Confusion Hyperreflexia( clonus(>3 beats)) Uterine tenderness or vaginal bleeding from a placental abruption Fetal growth restriction(esp. <36 weeks)

 Preicteal:
20% of women has no prodromal symptoms Some women may experience some signs and symptoms of

sever pre-eclampsia
Icteal:
Starts with face twitching Entire body becomes rigid Face is distorted, eyes protrude, arms are flexed, hands

clenched and legs are inverted Lasts approx. 15 -20 seconds Jaws open and close violently followed by muscles of the body contracting and relaxing (lasts approx. 1 minute) Patient then takes a long, deep stertorous breath and breathing is resumed

 Mild pre-eclampsia
Systolic blood pressure of >140mmHg on two occasions at

least 6 hours apart Proteinuria of > 300mg in 24 hours (1+ or greater on dipstick testing)
Severe pre-eclampsia
Systolic Blood pressure of >160 mmHg on two consecutive

occasions, six hours apart Proteinuria >3g in 24 hours (>3+ on dipstick) Oliguria Cyanosis as a result of Pulmonary Edema Symptoms of impending eclampsia Features of HELLP syndrome

Pre-eclampsia is the leading cause of mortality and morbidity to both mother and newborn.

Epidemiology

With respect to Trinidad, the hypertensive diseases account for 70% of all maternal deaths in contrast to 2% in the UK.

The incidence of eclampsia is about 1 to 3 per 1000 pregnancies.

In the UK it is rare with a prevalence of about 1:3000 pregnancies probably attributed to better antenatal care and more aggressive treatment of pre-eclampsia.

Mechanism is unclear but there are various theories. Factors to be considered are: 1) Abnormal placentation 2) Endothelial dysfunction 3) Maternal immunologic intolerance 4) Genetic, nutritional and environmental factors. 5) Cardio-renal changes 6) Minor factors

Major cause of the hypertension associated with pre-eclampsia.

Abnormal Placentation

Basically:
1)

Subset of cytotrophoblasts i.e. Invasive trophoblasts which invade the decidual spiral arteries. Invasion would lead to molecular changes which involves a change in morphology from small muscular arterioles to large capacitance low resistance vessels.

2)

3)

These changes will not be present with incomplete invasion resulting in vessels capable of vasoconstriction.

 Evidence points to failure of a second wave of

trophoblast invasion during 16-20 weeks. The trophoblast are responsible for the the breakdown of the muscularis layer of the spiral arterioles. Thus as fetoplacental metabolic demands increase, the spiral arterioles are unable to accomadate such the necessary increase in blood flow.

Incomplete invasion of spiral arteries

Placental hypoperfusion

Release of systemic vasoactive compounds

Exaggerated inflammatory response, vasoconstriction, * endothelial damage and platelet dysfunction.

Multiple organ dysfunction

 Integral in the development of pre-eclampsia

Endothelium secretes various vasoconstrictors such as

endothelin and thromboxane as well as vasorelaxants e.g. Nitric oxide and prostacyclin. In pre-eclampsia there is increased sensitivity to vasopressors due to reduced production of nitric oxide. Also the balance is in favour of thromboxane.

 Represents a dysregulation of maternal tolerance to

paternally derived placental and fetal antigens. Maternal-fetal immune maladaptation is characterised by defective cooperation between uterine NK cells and fetal HLA.

 This pathway culminates in the production of

aldosterone as a result of angiotensin II. Angiotensin II is a potent vasoconstrictor. Usually, in pregnancy, there is refractoriness to angiotensin II. This is not seen in pre-eclampsia. The result is vasoconstriction with a resulting increase in the total peripheral resistance hence an increase in BP.

 Pre-eclampsia is shown to involve multiple genes.

There are over 100 maternal and paternal genes which

have been studied in associated with pre-eclampsia as well as vascular disorders, blood pressure regulation, diabetes mellitus etc. This is substantiated by the fact that pre-eclampsia is positively correlated between close relatives i.e. seven fold risk in daughters with a mother having preeclampsia. However, some sources indicate that it may be due to a single recessive gene.

 Tumour necrosis factor Interleukins

Syncytial knots

 The progression from pre-eclampisa to eclampsia

could be viewed as a continuous spectrum with a bridging phase.

Preeclampisa

Impending Eclampsia

Eclampsia

 Eclampsia may represent the end stage of two different

pathophysiological processes.
1) Low cerebral perfusion as a result of vasospasm 2) Increased cerebral perfusion due to abnormalities in

autoregulation i.e. Endothelial dysfunction.

Cerebral vasospasm

Cerebral hypoxia

Cerebral oedema

Cerebral hypoxia which would lead to cerebral ischaemia.

Cerebrovascular haemorrhage

 History

Elevated mid-pregnancy blood pressure

Roll over test Doppler ultrasound

 Consider the extremes of reproductive age i.e. <16 of age or

>35 Past history of pre-eclampisa Nulliparity Poor prenatal care Chronic hypertension or renal disease Obesity Sickle cell disease Hyperplacentosis e.g. Clinical diabetes mellitus, gestational diabetes, hydatidiform mole, multiple pregnancy. Low socio-economic status.

 Simple, rapid, easy to perform, inexpensive and

noninvasive. Roll over test based on supine hypertension response. Done between the 28th and 32nd week of gestation.

Blood pressure measured in the left lateral position until stable.

Patient is rolled to the supine position and BP is measured immediately.

BP is also measured 5 minutes later

High sensitivity and specificity .

If there is a rise of 20mmHG or more in the diastolic blood pressure this is a postive supine pressor test.

 Waveforms are recorded from the maternal arcuate

arteries, which are the first branches of the uterine arteries. Failure of invasion results in a persistence of a high resistance waveform i.e. A notch rather than the development of the usual low resistance waveforms which are the end diastolic frequencies.

Moderate notching

Severe notching

 AIMS OF TREATMENT
TO CONTROL BLOOD PRESSURES TO PREVENT THE

DEVELOPMENT OF ANY COMPLICATIONS OF PREECLAMPSIA AND ECLAMPSIA

TO DETECT ANY IMPAIRMENT OF FETAL WELL-BEING TO DELIVER THE FETUS BY THE SAFEST AND MOST

EXPEDITIOUS MEANS AS WELL AS MAITAINING MATERNAL WELL-BEING

 Prevention of preeclampsia women at risk: multifetal gestation, vascular or renal disease, previous severe preeclampsia-eclampsia, abnormal uterine artery Doppler velocimetry antihypertensive drugs magnesium Zinc calcium low-dose aspirin (75mg po od) from 14 weeks (CLASP Trial)

 Mild preeclampsia - management

< 37 weeks gestation inpatient or outpatient management worsening disease: delivery, magnesium sulfate
> 40 weeks gestation delivery, magnesium sulfate 37 - 39 weeks gestation inducible cervix: delivery, magnesium sulfate cervix not inducible: inpatient or outpatient management

 Severe preeclampsia - expectant management

gestational age: not recommended for < 24 weeks or >

34 weeks gestation hospitalization: tertiary care center antenatal testing: daily

 Severe preeclampsia - guidelines for expedient

delivery
maternal indications eclampsia, thrombocytopenia, pulmonary edema, acute renal failure persistent severe headache or visual changes elevated liver enzymes with persistent severe epigastric pain or right upper quadrant tenderness labor or rupture of membranes vaginal bleeding, abruptio placenta

 Severe preeclampsia - guidelines for expedient

delivery
fetal indications repetitive severe variables or late decelerations biophysical profile < 4 on two occasions 4 hours apart amniotic fluid index < 2 cm intrauterine growth restriction fetal death > 34 weeks gestation

 Severe preeclampsia - management protocol

admission to labor and delivery for 24 hours
magnesium sulfate IV for 24 hours antihypertensives if diastolic blood pressure

> 110

mmHg meet guidelines for expedited delivery?

yes? Delivery

NOTE: SYNTOMETRINE IS CONTRAINDICATED

 Severe preeclampsia - management protocol

Expedited delivery? no? < 23 weeks: counseling for termination of pregnancy 23-32 weeks: steroids, antihypertensive medications, daily maternal and fetal evaluation, delivery at 34 weeks 32-33 weeks: amniocentesis
immature fluid - steroids, delivery in 48 hours

 May be maternal or fetal

Eclampsia is one of the most detrimental

complications and affects both the mother and fetus Most women make a full recovery, however, though small there is a risk of permanent disability or brain damage if convulsions are severe. Around 1 in 50 eclamptic mothers die from the condition During a seizure, unborn babies may suffocate and 1 in 14 may die

 HELLP Syndrome- combined liver and blood clotting

disorder Most likely to occur immediately after delivery but can appear anytime after 20 wks pregnancy or rarely before Potentially as serious as eclampsia but slightly more common Potential treatment is delivery of the baby with main danger to baby from premature birth

 Cerebral haemorrhage (more commonly stroke)

Blood clotting disorder- thrombocytopenia is the most

frequent coagulation abnormality but full picture of DIC not usually observed

 Organ problems:

- Acute renal failure

- Cardiac failure - Pulmonary edema

- Adult respiratory distress syndrome

- Hepatic rupture- rarely

 IUGR

Increased perinatal mortality and morbidity

Complications of sequale of prematurity

Aim:

1- Maintain patent airways and stabilise the patient 2- Stop and Prevent the fits 3- Administer Anti-hypertensives 4- Deliver in the the safest and most expeditious means to the mother

1. 2. 3.

Usually unnecessary to try to stop the initial convulsion which usually last about 60-90 seconds IV Diazepam slowly 5mg over 1 min Roll the patient on his left side to avoid maternal injury

Management of ECLAMPSIA
4. Apply Suction to the secretion from her mouth 5. Adequate Oxygen should be maintained by face mask & airways to prevent swallowing of tongue 6. Prevent further convulsions by MgSO4 by IV bolus of 4 6 g over 15 min. If convulsion recur further bolus of 2g. (According to Magpie Trial) 7. Acidosis should be corrected if necessary by IV NaHCO3 8. SBP 170 mmHg or more, DBP 110 mmHg is risk factor for CVA so should be lowered by either Nifedipine 10 20 mg SL. Or Hydralazine 5mg followed by infusion.

Management of ECLAMPSIA
Eclampsia - anticonvulsant therapy
magnesium sulfate mechanism of action - smooth muscle relaxation by displacement of calcium dosage - 4-6 g intravenous loading dose, followed by 2 g per hour may be given intramuscularly

Management of ECLAMPSIA
Eclampsia - magnesium sulfate
side effects: maternal hypotonia respiratory depression cardiac arrest neonatal depression
contraindicated in myasthenia gravis use with caution in renal insufficiency

Management of ECLAMPSIA
Eclampsia - anticonvulsant therapy
phenytoin used extensively in Europe may be used in myasthenia gravis mechanism of action - may increase gamma aminobutyric acid-mediated chloride conduction in postsynaptic membranes may inhibit neurotransmitter inhibitory systems

Management of ECLAMPSIA
Eclampsia - phenytoin
dosage - 1 g loading dose over 1 hour
cardiac monitoring during administration side effects arrhythmias with rapid administration hepatitis Steven-Johnson syndrome

Management of ECLAMPSIA
Eclampsia - anticonvulsant therapy
diazepam useful for status seizures mechanism of action - facilitate the binding of GABA to its receptor
benzodiazepine receptors

dosage - 10 mg at a rate of 5 mg per min may be repeated at 10 to 15 minute intervals

Management of ECLAMPSIA
Eclampsia - diazepam
side effects - loss of consciousness, hypotension,

respiratory depression caution - may increase risk of aspiration causes prolonged depression of the neonate
sodium thiopentotal
long acting barbiturate used when sedation, paralysis and intubation needed

Management of ECLAMPSIA
Eclampsia - which anticonvulsant to use?
magnesium is associated with decreased recurrence

risks of seizures when compared with diazepam or phenytoin diazepam is associated with increased need for mechanical ventilation

Management of ECLAMPSIA
Eclampsia - management of fetus
fetal bradycardia during seizure ~ 5 minutes after the onset of the seizure may be associated with rebound tachycardia recovery phase may show late decelerations monitor for uterine hypertonicity allow for fetal recovery monitor for signs of abruption

Management of ECLAMPSIA
Eclampsia
delivery is indicated regardless of gestational age
immediate cesarean delivery is not necessary

1.Insert canula size 10 2.Send blood to Lab for Hb, blood group, Platelet count, RFT, LFT, Uric acid concentration, coagulation study, RBS 3.Urine catheter (to urine output & protein)

1.Assessment of state of fetus (U/S, Doppler CTG) 2.either : - Deliver the baby regardless of the gestational age intense monitoring maternal health in hope of improvement fetal outcome by increase gestational age.

It is attention to fluid balance , BP , Renal & Hepatic function & CNS 1.More aggressive control of BP 2.MgSO4 maintained for 48 hrs at 1g/hr iv 3.Subcutaneous heparin prophylaxis

 Roopnarinesinghs Textbook of Obstetrics, 2008, 3rd

edition, Published by Lexicon Trinidad Ltd, 2008. p6188. Lecture Notes in Obstetrics and Gynaecology, 2004, 2nd edition, published by Blackwell Publishing Ltd, 1999. p122-127. Collins S. et al. Oxford Handbook of Obstetrics and Gynaecology 2nd ed. p62-68. Strikes Like Lightning: An EMS Case Review on Preeclampsia & Eclampisa, Anne Clouatre, 2009, Parker Emergency Medical Services.

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