DR. Mazin Daghestani

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Scientific Evolution - PastScientific Evolution - Past 17th AD : Eclampsia - a Greek word meaning ' to shine forth '-

related to visual phenomenon associated with PE.

Alexander Hamilton (1781) described eclampsia as a condition associated with seizures.

Bright in 1827 recognized albuminurea in addition, dropsy, relating it to renal disease and eclampsia.

In 1896 when the sphygmomanometer was invented, arterial hypertension was found associated with eclampsia

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The cornerstone of therapy for this multisystem disorder is delivery of the baby

The incidence of eclampsia in the developed countries is 1:2000 deliveries. while in developing countries estimate vary widely, from 1 in 100 to 1 in 1700 deliveries .

The incidence of eclampsia in Makkah is 1 in 520 deliveries

Forty-four percent of seizures occur postnatally, the remainder being antepartum (38%) or intrapartum (18%).

The maternal case fatality rate is 1.8% (3.9 % in Makkah ) and 35% of women will have at least one major complication.

Eclampsia is among the leading causes of maternal mortality worldwide

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By definition, 2 or more of the following features must also be present within 24 hours of the seizure:[

•hypertension •proteinurea •thrombocytopenia •elevated serum AST levels.

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Eclampsia collaborative trial in UK:

85% of patients seen 7 days before the eclamptic fit

11% no hypertension or proteinurea

10% proteinurea but, NO hypertension

22% hypertension but, NO proteinurea

57% hypertension and proteinurea

Douglas & Rodman BMJ (309) 1994

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It is extremely difficult to predict which women with pre-eclampsia will develop eclamptic seizures. Consequently, it is almost impossible to devise strategies for seizure prophylaxis in pre-eclamptic women.

Although this has been recently answered in the “Magpie” trial which showed clear advantages in the use of Magnesium Sulfate in severe pre-eclampsia reduced the relative risk of eclampsia by 58% (0.8% vs. 1.9%, P < .0001) and of maternal death by 45% (0.2% vs. 0.4%,

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Drug of choice is Magnesium Sulfate

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Magnesium sulphate is the anticonvulsant of choice for women with eclampsia. Lytic cocktail should be abandoned

Magnesium sulphate versus lytic cocktail for eclampsia

The Cochrane Library, Issue 2 2003

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Magnesium sulphate versus diazepam for eclampsia

“Magnesium sulphate appears to be substantially more effective than diazepam for treatment of eclampsia”

The Cochrane Library, Issue 2 2003

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How Does it Work?

Magnesium sulfate is not a conventional anticonvulsant agent and its mechanism of action in eclampsia is not well understood. Eclampsia is thought to occur secondary to ischaemia caused by cerebral vasospasm.[Magnesium sulfate is a potent vasodilator, particularly in the cerebral vasculature.In women with pre-eclampsia, magnesium sulfate has been shown to improve cerebral arterial circulation, and preclinical evidence suggests possible neuroprotective effects

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Pritchard's and Zuspan's regimens for magnesium sulfate administration in eclampsia[

Pritchard's regimen

Loading dose: 4g IV (administered over 5 to 10min; concentration not to exceed 20%a ) plus 10g IM (using undiluted 50% solution)

Maintenance dose: 5g IM q4h x >/=24h after the last seizure (using undiluted 50% solution administered in alternate buttocks)

Zuspan's regimen

Loading dose 4g IV (administered over 5 to 10min; concentration not to exceed 20%a)

Maintenance dose: 1 to 2 g/h by controlled infusion pump x >/=24h after the last seizure (concentration not to exceed 20%a )

aLower concentrations, e.g. 10%, are preferred.

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Eclamptic seizure identified

Diazepam 5mg IV repeated as needed up to 20 mg to stop seizure

Secure airway

Place patient in recovery position

Facial oxygen

Contraindication to magnesium sulphate?

Heart block

H/o myocardial infarction

Consider alternative agents (diazepam or thiopentone)

Provide supportive therapy(maintain fluid balance, blood pressure control, etc..)

Once seizures are controlled, blood pressure is sustained and hypoxia corrected, delivery can be expedited in applicable cases

Yes

No

Start magnesium sulfate therapy

Provide supportive therapy(maintain fluid balance, blood pressure control, etc..)

Once seizures are controlled, blood pressure is sustained and hypoxia corrected, delivery can be expedited in applicable cases

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Monitor patellar reflex & respiratory rate at hourly intervals

Regular monitoring of serum Mg Sulfate, particularly in women with renal disease, output <100 ml/4 hours. Therapeutic range 2-4 mmol/l

Signs of hypermagnesaemia?

Respiratory rate <16/min

Knee jerk reflexes absent

Continue mag. sulfate

Withhold further Mg sulfate until signs of hypermagnesaemia resolve

Significant respiratory depression will require calcium gluconate IV

Clinical signs of hypermagnesaemia resolves

Recurrent seizures?

Continue mag. Sulfate for 24 hours after last seizure

Mg sulfate 2 gm Iv over 5-10 min and continue maintenance dose

Repeated seizures?

No

Yes

No

No

Yes

Consider alternative agents ( diazepam or thiopentone)

Yes

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Dose alteration:

Oligurea: <100 ml/4hrs or urea >10 mmol/l … give 1 gm/h maintenance… frequent levels

ALT: 250 iu/l.. Measure Mg levels every 2-4 hrs

Mg level> 4 mmol/l: decrease maintenance dose to 0.5-1 g/h

Mg level< 1.7 mmol/l: 2 gm IV bolus over 20 min and increase maintenance dose to 2.5g/h

No reagent for levels: maintenance dose of 0.5 g/h and R.R + Knee reflexes monitoring

Toxicity:

5 mmol/l: loss of patellar reflex, weakness, nausea, double vision

6-7.5 mmol/l: muscle paralysis and respiratory arrest

> 12 mmol/l: cardiac arrest

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The maternal risks of cerebrovascular accident and of left ventricular or renal failure begin to increase significantly when hypertension is severe .

Reduction of severe hypertension (blood pressure > 160/110 mm Hg or mean arterial pressure > 125 mm Hg) is mandatory to reduce the risk of cerebrovascular accident. Treatment may also reduce the risk of further seizures

M.A.P.=SBP -DBP +DBP

3

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Findings of randomized trials have suggested that nifedipine and labetalol are superior or equivalent to hydralazine for severe hypertension in pregnancy

researchers found neuromuscular blockade, potent hypotension, and cardiac toxicity when nifedipine was used with anticonvulsant magnesium sulphate

the choice of which to use is likely to depend on personal preference and availability

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Associated complications include haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (3%), disseminated intravascular coagulation (3%), renal failure (4%) and adult respiratory distress syndrome (3%).

Frequent monitoring of haemoglobin, platelet count, transaminases, urea and creatinine together with oxygen saturation is therefore necessary.

Cerebral imaging (MRI or CT) is not indicated in uncomplicated eclampsia. However, imaging is necessary to exclude haemorrhage and other serious abnormalities in women with focal neurological deficits or prolonged coma

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*The definitive treatment of eclampsia is delivery. Attempts to prolong pregnancy in order to improve fetal maturity are unlikely to be of value. However, it is inappropriate to deliver an unstable mother even if there is fetal distress. Once seizures are controlled, severe hypertension treated, and hypoxia corrected, delivery can be expedited.

*Vaginal delivery should be considered but caesarean section is likely to be required in primigravidae remote from term with an unfavourable cervix.

*After delivery, high dependency care should be continued for a minimum of 24 hours

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Methods Used to Prevent Hypertensive Disorders of Pregnancy

 Proper prenatal care  Low-salt diet  Diuretics  Antihypertensive drugs  Nutritional supplementation

  Magnesium (365 mg/d)  Zinc (20 mg/d)  Calcium (1500–200 mg/d)  Fish oil

 Antithrombotic agents   Low-dose aspirin (50–150 mg/d)  Dipyridamole (225–300 mg/d)  Subcutaneous heparin (15,000 IU/d)

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“Low doses of aspirin do help prevent pre-eclampsia, but there is little information about whether they are of benefit for treatment of established pre-eclampsia “ cochrane 22 April 2003

Pre-eclampsia is a condition in pregnancy involving high blood pressure and protein in the urine. It can lead to serious complications and death. As pre-eclampsia affects blood clotting, antiplatelets (drugs like aspirin which can prevent blood clots) are used for pre-eclampsia. The review of trials found that low doses of aspirin lowered the risk of pre-eclampsia a little (15% lowering in the risk), with a similar lowering in the risk of the baby dying (14%) and a very small lowering in the risk of the baby being born too early (8%). Doses less than 75mg appear to be safe. Higher doses may be better, but as the risks of adverse effects may also increase, more research is needed.

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“Calcium supplements may prevent high blood pressure and help prevent preterm labour”

cochrane 22 April 2003

Reviewers' conclusions:

Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. Optimum dosage requires further investigation.

Main results:

Eleven studies were included, all of good quality. There was a modest reduction in high blood pressure with calcium supplementation . The effect was greatest for women at high risk of hypertension (relative risk 0.45, 95% confidence interval 0.31 to 0.66) and those with low baseline dietary calcium (relative risk 0.49, 95% confidence interval 0.38 to 0.62).

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Regular F/U at ANC

Paramedical care and transport facilities

Prompt action in severe PE

Proper use of Mg Sulfate prophylaxis

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eclampsia is one of the leading causes of maternal death

it is poorly respected in our practice, despite being commoner than international figures due to multi-ethnic origins in Makkah.

team work is needed to ensure success of treatment

written and will rehearsed protocol is mandatory

central/ regional centre with full facilities and expertise for referrals and consultation.

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HELLP SYNDROME ABRUPTIO PLACENTAE PULMONARY OEDEMA ACUTE RENAL FAILURE CEREBRAL HAEMORRHAGE VISUAL DISTURBANCES & BLINDNESS HEPATIC RUPTURE ELECTROLYTIC IMBALANCE POSTPARTUM COLLAPSE

SERIOUS COMPLICATIONS: -

HELLP Syndrome as a HELLP Syndrome as a separate entity separate entity

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HELLP, a syndrome characterized by

hhemolysis, emolysis, eelevated levated lliver enzyme iver enzyme levels and a levels and a llow ow pplatelet countlatelet count, is an obstetric complication that is frequently misdiagnosed at initial presentation. Many investigators consider the syndrome to be a variant of preeclampsia,

but it may be a separate entity.

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In some cases , HELLP symptoms are the first warning of preeclampsia and the condition is misdiagnosed as hepatitis, idiopathic thrombocytopenic purpura, gallbladder disease, or thrombotic thrombocytopenic purpura.

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Epidemiology and Risk FactorsEpidemiology and Risk Factors

HELLP syndrome 0.2 to 0.6 % of all pregnancies. Preeclampsia 5 to 7 % of all pregnancies.

Superimposed HELLP syndrome develops in 4 to 12 percent of women with preeclampsia or eclampsia.

Wolf JL. Liver disease in pregnancy. Med Clin North Am 1996.

Maternal mortality has been estimated to be as high as 2-24%

Perinatal mortality is equally high, ranging from 9 –39 %.

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The hemolysis in HELLP syndrome is a microangiopathic hemolytic anemia. Red blood cells become fragmented as they pass through small blood vessels with endothelial damage and fibrin deposits.

The peripheral smear may reveal spherocytes, schistocytes, triangular cells and burr cells.

increase in Bilirubin and lactic dehydrogenase levels.

Etiology and PathogenesisEtiology and Pathogenesis

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The elevated liver enzyme levels in the syndrome are thought to be secondary to obstruction of hepatic blood flow by fibrin deposits in the sinusoids. This obstruction leads to periportal necrosis and, in severe cases, intrahepatic hemorrhage, subcapsular hematoma formation or hepatic rupture.

Etiology and PathogenesisEtiology and Pathogenesis

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The thrombocytopenia has been attributed to increased consumption and/or destruction of platelets.

With platelet activation, thromboxane A and serotonin are released, causing vasospasm, platelet agglutination and aggregation, and further endothelial damage.

Etiology and PathogenesisEtiology and Pathogenesis

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Clinical PresentationClinical Presentation

90%of patients present with generalized malaise,

65 % with epigastric pain, 30 % with nausea and vomiting,31 percent with headache.

All are nonspecific symptoms

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Because of the variable nature of the clinical presentation, the diagnosis of HELLP syndrome is generally delayed for an average of eight days.

Usually presented by complicationsUsually presented by complications

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In one retrospective chart review of patients with HELLP syndrome, only two of 14 patients entered the hospital with the correct diagnosis.

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Because early diagnosis of this syndrome is critical, any pregnant woman who presents with malaise or a viral-type illness in the third trimester should be evaluated with a complete blood cell count and liver function tests.

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Clinical PresentationClinical Presentation

The physical examination may be normal in patients with HELLP syndrome.

1- right upper quadrant tenderness 90 %2- Edema is not a useful marker 3- Hypertension and proteinuria may be absent or mild.

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DiagnosisDiagnosis

Martin JN Jr, Rinehart BK, May WL, Magann EF, Terrone DA, Blake PG.

There is agreement among most of the authors that, the diagnosis requires the concurrence of hemolysis, elevated liver enzymes, and low platelet count. However, there is obviously still a lack of consensus on the laboratory parameters and their cutoff values used to diagnose

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Laboratory Diagnostic Criteria for Laboratory Diagnostic Criteria for HELLP syndromeHELLP syndrome

Haemolysis Abnormal peripheral smear : spherocytes, schistocytes,

triangular cells and burr cells Total Bilirubin level > 1.2 mg/dL Lactate dehydrogenase level > 600U/L

Elevated liver function test result Serum aspartate amino transferase level > 70U/L Lactate dehydrogenase level >600 U/L

Low platelet count Platelet count < 150 000/mm3

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Platelet countPlatelet count appears to be the

most reliable indicator of the

presence of HELLP syndrome

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Clinical utility of strict diagnostic Clinical utility of strict diagnostic criteria for the HELLPcriteria for the HELLP

the use of strict diagnostic criteria in the definition of the HELLP syndrome allows for greater prediction of complication rates. and define the cases that are Eligible to conservative management

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ClassificationClassification

full HELLP syndrome

partial HELLP syndrome

based on the number of abnormalities

Audibert F, Friedman SA, Frangieh AY, Sibai BM. Am J Obstet Gynecol 1996; 175:460-4 .

considered for delivery within 48 hours

candidates for more conservative management

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ClassificationClassificationon the basis of platelet

count

class I, less than 50,000 per mm3less than 50,000 per mm3

class II, 50,000 to less than 100,000 per mm350,000 to less than 100,000 per mm3

class III, 100,000 to 150,000 per mm3100,000 to 150,000 per mm3

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Management

CorticosteroidsMagnesium sulphate

Hypotensive drugsBlood products

Delivery

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The treatment approach should be based on the estimated gestational age and the condition of the mother and fetus.

Prolongation of pregnancy, in theory, may be favourable for the foetus whereas it remains controversial whether maternal condition is further deteriorated by expectant management

Visser W, Wallenburg HC. Temporising management of severe pre-eclampsia with and without the HELLP syndrome. Br J Obstet Gynaecol 1995;102:111-7

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hypertension is controlled at less than 160/110 mm hg,

Oliguria responds to fluid management .

Elevated liver function values are not associated with right upper quadrant or epigastric pain.

Class II –III .(platelet count).>50000

Eligibility to conservative management

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The Cochrane Library holds two protocols which when complete may summarize evidence to date on the use of corticosteroids for HELLP syndrome . and interventionist versus expectant management of severe pre-eclampsia before term.

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The antenatal administration of dexamethasone (Decadron) in a high dosage of 10 mg intravenously every 12 hours has been shown to markedly improve the laboratory abnormalities associated with HELLP syndrome.

Steroids given antenatally do not prevent the typical worsening of laboratory abnormalities after delivery. However, laboratory abnormalities resolve more quickly in patients who continue to receive steroids postpartum.

Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN Jr. Am J Obstet Gynecol 1994;171:1148-53.

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Corticosteroid therapy should be instituted in patients with HELLP syndrome who have a platelet count of less than 100,000 per mm3 .And should be continued until liver function abnormalities are resolving and the platelet count is greater than 100,000 per mm3

Magann EF, Perry KG Jr, Meydrech EF, Harris RL, Chauhan SP, Martin JN Jr. Am J Obstet Gynecol 1994;171:1154-8.

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Intravenously administered dexamethasone appears to be more effective than intramuscularly adminstered betamethasone for the antepartum treatment of mothers with HELLP syndrome.

(Am J Obstet Gynecol 2001;184:1332-9.).

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Administration of glucocorticoids increases the use of regional anesthesia in women with antepartum HELLP syndrome who have thrombocytopenia.

(Am J Obstet Gynecol 2002;186:475-9.).

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Patients treated with dexamethasone exhibit longer time to delivery; This facilitates maternal transfer to a tertiary care center and postnatal maturity of fetal lungs

(Am J Obstet Gynecol 2002;186:475-9.).