DR. SUMIT KAMBLESENIOR RESIDENT

DEPT. OF NEUROLOGYGMC, KOTA

PREECLAMPSIA

New onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman

Criteria for the diagnosis of preeclampsia

Systolic blood pressure ≥140 mmHgOr

Diastolic blood pressure ≥90 mmHgAnd

Proteinuria ≥0.3 grams in a 24-hour urine specimen

Sibai b et al. Preeclampsia. Lancet.2005;365:785-799

Eclampsia – Occurrence of one or more generalized

convulsions and/or coma in the setting of preeclampsia and in the absence of other neurologic conditions.

Sibai b et al. ACOG. Diagnosis, prevention and mm of eclampsia;.2005;402-410

Eclamptic seizure occurs in 2-3 % ofseverely preeclamptic women not receivinganti-seizure prophylaxis;

Incidence of eclampsia in developingcountries varies widely: from 6 to 157 casesper 10,000 deliveries

Approximately one maternal death due to eclampsia per 100,000 live births

case-fatality rate of 6.4 deaths per 10,000 cases

Geographic variation in the incidence of hypertension in pregnancy. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Am J Obstet Gynecol 1988; 158:80.

Lubarsky SL, Barton JR, Friedman SA, et al. Late postpartum eclampsia revisited. Obstet

Gynecol 1994; 83:502

Nulliparity Preeclampsia in a previous pregnancy Age >40 years or <18 years Family history of preeclampsia Chronic hypertension Chronic renal disease Antiphospholipid antibody syndrome or inherited

thrombophilia Vascular or connective tissue disease Diabetes mellitus (pregestational and gestational) Multifetal gestationHigh body mass index

Black race Hydrops fetalis Unexplained fetal growth restriction Fetal growth restriction, abruptio placentae, or fetal demise in a previous

pregnancy Prolonged interpregnancy interval Partner related factors (new partner, limted sperm

exposure [eg, previous use of barrier contraception]) Hydatidiform mole Susceptibility genes

Symptoms: •Headache •Visual disturbance •Epigastric pain •Nausea •Restlessness •Swelling •Poor urine output

signs: •Agitation •Hyperreflexia •Facial &peripheral

oedema •Rt upper quadrant

tendernes

Features of pre-eclampsia plus one the following:

– Systolic bp>160 mmHg –Diastolic bp>110mHg –Proteinuria> 5g per 24 hours –Cerebral or visual disturbances: headache, tinnitus, –Oliguria< 500ml per 24 hours, creatinine>1.2mg/dl –Epigastric pain –Pulmonary oedema –Heamolysis, elevated liver enzymes and low platalet syndrome=

HELLP syndrome –Fetal criteria-IUGR, oligohydro, fetal death

ACOG,PracticeBull.2002

•Cerebrovascular accidents •Hypertensive encephalopathy •Seizure disorder •Previously undiagnosed brain tumors •Metastatic gestational trophoblastic disease •Metabolic diseases- hyponatremia, hypoglysemia

•Reversible posterior leukoencephalopathysyndrome

•Cerebral vasculitis Sibai E. Diagnosis and management of eclampsia. ACOG 2005

Headache- temporal, frontal, occipital, or diffuse

Generalized hyperreflexia; sustained ankle clonus may be present.

Visual symptoms - include blurred vision, flashing lights (photopsia), and scotomata . Diplopia or amaurosis fugax may also occur.

Cortical blindness is rare .

Blindness related to retinal pathology, optic nerve damage, retinal artery spasm, and retinal ischemia, may be permanent

Seizures

Posterior reversible leukoencephalopathysyndrome (PRES)

Stroke leading to death or disability is the most serious complication

Cerebral overregulation results in vasospasm of cerebral arteries, underperfusion of the brain, localized ischemia/infarction, and cytotoxic (intracellular) edema.

Loss of autoregulation of cerebral blood flow (ie, hypertensive encephalopathy) results in hyperperfusion, endothelial damage, and vasogenic (extracellular) edema.

Morriss MC, Twickler DM, Hatab MR, et al. Cerebral blood flow and cranial magnetic resonance imaging in eclampsia and severe preeclampsia. ObstetGynecol 1997; 89:56

General principles- The immediate issues in caring for an

eclamptic woman include:

1. Prevention of maternal hypoxia and trauma2. Management of severe hypertension, if

present3. Prevention of recurrent seizures4. Evaluation for prompt delivery.

Maternal assessment should include:–History and examination: BP, weight gain,

edema, sensorium–Serial or continuous blood pressure

monitoring–Urinanalysis for proteinuria–quantification for degree of severity

–Blood test include•Platelet count and morphology, CBC•Haemocoagulation system: PT, aPTT•Uric acid, creatinin, electrolytes for renal

function•Serum uric acid –useful early and for

progression•Hepatic enzymes (AST,ALT,GGT)& bilirubin

–Fluid balance –urine output, CVP, SP02 etc–ECG

•Cerebral imaging is not necessary for the diagnosis and management of most women with eclampsia.

•Cerebral imaging findings in eclampsia are similar to those found in patients with hypertensive encephalopathy.

Cerebral imaging is indicated :-

•focal neurologic deficits •prolonged coma •atypical presentation for eclampsia: •onset before 20 weeks of gestation or •more than 48 hours after delivery •eclampsia refractory to adequate mgso4 therapy

Sibai BM. Hypertension and Obstetrics. Churchill Livingstone. 2002

•Fetal monitoring:–

-Cardiotocography–for acceleration, loss of variability or decelerations

–Fetal ultrasound -may be useful for fetal size and morphology, amniotic fluid volume estimation

–Placental and fetal blood flow measurement of uterine artery and main fetal Doppler velocimetry(including diastolic flow)

Treatment required when:–Systolic bp> 160 mm Hg orDiastolic bp> 110 mm Hg

Hydralazine: agent of choice(5-10mg IV max30)

–Causes direct arteriolar vasodilation–Improves renal and uteroplacental blood flow

•Labetalol: causes rapid decrease in arterial bp without compromising uteroplacental flow–May cross placenta but fetal complications rare–20-40mg every 30min for a max of 220mg IV

Nifedipine: oral 10-20mg every 30min for a max of 50mg

-causes direct relaxation of arteriolar smooth muscle

–Maintains uterine perfusion–Can cause uterine muscle relaxation–increase risk of post partum haemorrhage–Relative contra-indication with use of Mg

•Sodium nitroprusside: hypertensive emergencies but should be avoided due to safety concern

•Nitroglycerin : useful especially when pulmonary oedema complicates situation

WHO recommmendations for prevention and treatment of PEC & EC 2011

Reasonable goal is systolic BP of 140 to 155 mmHg and diastolic BP of 90 to 105 mmHg.

In women with extremely severe hypertension (≥180/120 mmHg), a diastolic goal of 100 to 105 mmHg should be achieved within two to six hours, with the maximum initial (within 10 to 20 minutes) fall in BP not exceeding 25 percent of the presenting value

Vaughan CJ, Delanty N. Hypertensive emergencies. Lancet 2000; 356:411. Ledingham JG, Rajagopalan B. Cerebral complications in the treatment of accelerated

hypertension. Q J Med 1979; 48:25

Use of antihypertensive agents to control mildly elevated blood pressure in the setting of preeclampsia/eclampsia has not been shown to alter the course of the disease, nor to diminish perinatal morbidity or mortality.

Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med 1996; 335:257. von Dadelszen P, Ornstein MP, Bull SB, et al. Fall in mean arterial pressure and fetal growth

restriction in pregnancy hypertension: a meta-analysis. Lancet 2000; 355:87. Magee LA, Ornstein MP, von Dadelszen P. Fortnightly review: management of hypertension in

pregnancy. BMJ 1999; 318:1332.

•Airway protection

•Maintain oxygenation(O2 inhalation via mask)

•Control of seizures–Continued convulsions may indicate other cerebral pathology–Management may involve treatment cerebral oedema

•Delivery of fetus when mother is in stable condition, even in some situation CS is needed acutely

•Magnesium sulphate: -anticonvulsant of choice

–Action by:•antagonism of calcium and hence decreased

systemic and cerebral vasospasm•Increase release of PGI2 by vascular endothelium

–Other effects in parturient include:•Tocolysis•Decreased cathecholamine release•Mild antihypertensive•Increases renal and uterine blood flow

–Renaly excreted–so reduce dose in renal failure

–Therapeutic level 4-7 mEq/l ; must monitor for toxicity

–Repeated seizures despite therapeutic levels need to consider other anticonvulasnts.

Regimen Loading Dose Maintenance Dose

Pritchard(Intramuscular)

4gm IV over 3-5 min f/b 10gm deep IM(5gm each buttock)

5gm IM 4 hourly in alternate buttock

Zuspan or Sibai(Intravenous)

4gm IV over 15-20 min.

1-2gm/hr IV infusion

4/2/2015Dutta’s. Hypertensive disorder of pregnancy: 17 29

•Hypotension, flushing, slurred speech, drowsiness, double vision

•Absent reflexes•Respiratory paralysis•Conduction (heart) disturbances•Cardiac arrest–Calcium Gluconate 1G slow

push –10 min

An additional benefit of magnesium sulfate therapy is in women expected to have a preterm delivery within 24 hours have consistently demonstrated a decreased risk of cerebral palsy and severe motor dysfunction in offspring

Crowther CA, Hiller JE, Doyle LW, et al. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA 2003; 290:2669.

Rouse DJ, Hirtz DG, Thom E, et al. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359:895.

• Additional bolus of 2 grams of magnesium sulfate over 15 to 20 minutes, with careful monitoring for signs of magnesium toxicity.

• Phenytoin : effective in pre-eclampsia–Central anticonvulsant activity–No effect on uterine tone, fetal HR or neonatal

tone

•Diazepam: effective especially if needed acutely but causes fetal/ neonatal complications(depression of muscle tone and breath centre)

The Eclampsia Trial Collaborative Group conducted two prospective trials

The primary outcome measures were the rates of recurrent seizures and maternal death.

Magnesium sulfate was significantly more effective than either diazepam or phenytoin:

Which anticonvulsant for women with eclampsia? Evidence from the Collaborative Eclampsia Trial. Lancet 1995; 345:1455.

Additional advantages of magnesium sulfate therapy include lower cost, ease of administration and less sedation .

Magnesium also appears to selectively increase cerebral blood flow and oxygen consumption in women with preeclampsia

Belfort MA, Moise KJ Jr. Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: a randomized, placebo-controlled study. Am J Obstet Gynecol 1992; 167:661.

Cerebrovascular syndromes and preeclampsia

RCVS (postpartum

angiopathy)

RPLS Preeclampsia,

severe

Ischemic

stroke

Reversible vasogenic edema, subarachnoid

hemorrhage

Thunderclap

headache, reversible cerebral vasoconstriction

Intracerebral hemorrhage

Most common causes of both ischemic and hemorrhagic stroke in pregnancy.

The most frequent cerebrovascular disturbance associated with eclampsia is a reversible encephalopathy.

Women with preeclampsia are at risk for stroke and cardiovascular disease well after the postpartum period and child bearing years. The relative risks ranged from 1.39 to 5.08.

B. J. Wilson, M. S. Watson, G. J. Prescott et al., “Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study,” British Medical Journal, vol. 326, no. 7394, pp. 845–849, 2003

-Preeclampsia/eclampsia commonly associated with ischemic stroke of arterial origin [36 percent])

-Intracerebral hemorrhage [55 percent]) but less frequently with cerebral venous thrombosis (13 of 136 cases [10 percent])

Cantu-Brito C, Arauz A, Aburto Y, et al. Cerebrovascular complications during pregnancy and postpartum: clinical and prognosis observations in 240 Hispanic women. Eur J Neurol 2011; 18:819

Is a clinical radiologic syndrome of heterogeneous etiologies that are grouped together because of similar findings on neuroimaging studies

RPLS may occur in the setting of preeclampsia due to impaired cerebral autoregulation from endothelial damage.

Autoregulatory failure Endothelial dysfunction

vasodilatation capillar leakage

hyperperfusion disruption BBB

Vasogenic edeoma

Clinical presentation Headaches Altered consciousness Visual disturbances Seizures - are usually generalized tonic

clonic; they may begin focally.

Other risk factors- Acute and chronic renal failure Immunosuppressive agents and cytotoxic drugs Hemolytic and uremic syndrome Collagen vascular disorders leukemia Behcets syndrome TTP HIV Acute intermittent prophyria Hypercalcemia,hypomagnesmia Contrast media exposure Cryoglobulinemia

Some suggest that PRES (typical clinical syndrome and neuroimaging findings) could be considered an indicator of eclampsia, even when the other features of eclampsia (proteinuria, hypertension) are not present.

Br J Obstet Gynaecol 1997 Oct;104(10):1165-72

FLAIR images show high signal symmetrically involving bilateral parieto-occipital, posterior frontal, and temporo-occipital regions

The classical presentation of RCVS, also known as Call Fleming Syndrome, is a thunderclap headache, with or without additional neurologic signs.

Diagnostic imaging reveals multifocal segmental vasoconstriction of the cerebral arteries, which usually resolves within days to weeks.

Calcium channel blockers may be initiated, such as nimodipine or verapamil, although caution should be employed to maintain cerebral perfusion in watershed regions of a constricted artery.

The primary difference between RPLS and RCVS is in the clinical symptoms.

L.H. Calabrese, D.W. Dodick, T. J. Schwedt, and A. B. Singhal, “Narrative review: reversible cerebral vasoconstriction syndromes,” Annals of Internal Medicine, vol. 146, no. 1, pp. 34– 44, 2007.

There is nearly a 4-fold odds of developing hypertension (OR 3.7, 95% CI 2.70–5.05)

2-fold risk of ischemic heart disease (OR 2.16, 95% CI 1.86–2.52) in women with preeclampsia.

For fatal and nonfatal stroke, relative risks ranged from 1.39 to 5.08.

Children may also be at increased risk for neurological problems and stroke.

There was a significant reduction in the rate of preeclampsia with low dose aspirin started at 16 weeks gestation or earlier in women identified as moderate or high risk.

Vitamin D deficiency has recently emerged as an important potentially modifiable risk factor for both preeclampsia and stroke.

E. Bujold, S. Roberge, Y. Lacasse et al., “Prevention of preeclampsia and intrauterine growth restriction with aspirin started in early pregnancy: a metaanalysis,” Obstetrics and Gynecology, vol. 116, no. 2 PART 1, pp. 402–414, 2010.