ECLAMPSIA DR. Mazin Daghestani

Scientific 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 13/12/2003

ECLAMPSIA Eclampsia is among the leading causes of maternal mortality worldwide 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. The cornerstone of therapy for this multisystem disorder is delivery of the baby 13/12/2003

ECLAMPSIA 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. 13/12/2003

ECLAMPSIA 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 13/12/2003

ECLAMPSIA 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%, 13/12/2003

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Treatment & Prphylaxis of Seizures Drug of choice is Magnesium Sulfate 13/12/2003

Treatment & Prphylaxis of Seizures Magnesium sulphate versus lytic cocktail for eclampsia Magnesium sulphate is the anticonvulsant of choice for women with eclampsia. Lytic cocktail should be abandoned The Cochrane Library, Issue 2 2003 13/12/2003

Treatment & Prphylaxis of Seizures 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 13/12/2003

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 13/12/2003

Treatment & Prphylaxis of Seizures 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. 13/12/2003

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Treatment & Prphylaxis of Seizures Eclamptic seizure identified Treatment & Prphylaxis of Seizures 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 13/12/2003

Treatment & Prphylaxis of Seizures 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 Withhold further Mg sulfate until signs of hypermagnesaemia resolve Significant respiratory depression will require calcium gluconate IV Yes No Continue mag. sulfate Clinical signs of hypermagnesaemia resolves Mg sulfate 2 gm Iv over 5-10 min and continue maintenance dose Yes Recurrent seizures? No Consider alternative agents ( diazepam or thiopentone) No Yes Continue mag. Sulfate for 24 hours after last seizure Repeated seizures? 13/12/2003

Dose alteration: Toxicity: 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 13/12/2003

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Treatment of Hypertension 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 13/12/2003

Treatment of Hypertension 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 13/12/2003

Anti-hypertension therapy 13/12/2003

Anti-hypertension therapy 13/12/2003

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Investigations 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 13/12/2003

Delivery *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 13/12/2003

Anesthesia protocol 13/12/2003

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Pre-eclampsia Eclampsia Prevention 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) 13/12/2003

Prevention “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. 13/12/2003

Prevention “Calcium supplements may prevent high blood pressure and help prevent preterm labour” cochrane 22 April 2003 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). 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. 13/12/2003

Prevention Regular F/U at ANC Paramedical care and transport facilities Prompt action in severe PE Proper use of Mg Sulfate prophylaxis 13/12/2003

Take home message 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. 13/12/2003

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SERIOUS COMPLICATIONS: - HELLP SYNDROME ABRUPTIO PLACENTAE PULMONARY OEDEMA ACUTE RENAL FAILURE CEREBRAL HAEMORRHAGE VISUAL DISTURBANCES & BLINDNESS HEPATIC RUPTURE ELECTROLYTIC IMBALANCE POSTPARTUM COLLAPSE 13/12/2003

HELLP Syndrome as a separate entity

but it may be a separate entity. HELLP, a syndrome characterized by hemolysis, elevated liver enzyme levels and a low platelet 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. 13/12/2003

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. 13/12/2003

Epidemiology 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. Maternal mortality has been estimated to be as high as 2-24% Perinatal mortality is equally high, ranging from 9 –39 %. Wolf JL. Liver disease in pregnancy. Med Clin North Am 1996. 13/12/2003

Etiology and Pathogenesis 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. 13/12/2003

Etiology and Pathogenesis 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. 13/12/2003

Etiology and Pathogenesis 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. 13/12/2003

Clinical 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 13/12/2003

Usually presented by complications 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 complications 13/12/2003

In one retrospective chart review of patients with HELLP syndrome, only two of 14 patients entered the hospital with the correct diagnosis. 13/12/2003

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. 13/12/2003

Clinical 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. 13/12/2003

Diagnosis 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 Martin JN Jr, Rinehart BK, May WL, Magann EF, Terrone DA, Blake PG. 13/12/2003

Laboratory Diagnostic Criteria for HELLP 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 13/12/2003

Platelet count appears to be the most reliable indicator of the presence of HELLP syndrome 13/12/2003

Clinical utility of strict diagnostic criteria 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 13/12/2003

based on the number of abnormalities Classification based on the number of abnormalities full HELLP syndrome partial HELLP syndrome considered for delivery within 48 hours candidates for more conservative management Audibert F, Friedman SA, Frangieh AY, Sibai BM. Am J Obstet Gynecol 1996; 175:460-4. 13/12/2003

on the basis of platelet count Classification on the basis of platelet count class I, less than 50,000 per mm3 class II, 50,000 to less than 100,000 per mm3 class III, 100,000 to 150,000 per mm3 13/12/2003

Management Delivery Corticosteroids Hypotensive drugs Blood products Magnesium sulphate Hypotensive drugs Blood products 13/12/2003

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 13/12/2003

Eligibility to conservative management 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 13/12/2003

Corticosteroids 13/12/2003

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. 13/12/2003

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. 13/12/2003

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. 13/12/2003

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.). 13/12/2003

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.). 13/12/2003

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.). 13/12/2003