1. PREECLAMPSIA Reinaldo Figueroa, MD Winthrop-University Hospital

2. PREECLAMPSIA Hypertensive disorder specific to pregnancy –affects nearly 6% of all pregnancies –a major cause of maternal and neonatal mortality and morbidity –15 to 20 % of maternal mortality in developed countries

3. PREECLAMPSIA Severity ranges from: –a mild disorder (transient hypertension in the later part of the pregnancy) to –a life-threatening disorder with seizures, HELLP syndrome, fetal hypoxia, and growth retardation more severe disease: 0.56 per 1000 deliveries

4. PREECLAMPSIA Predisposes women to other serious complications: –placental abruption –acute renal failure –cerebral hemorrhage –disseminated intravascular coagulation –circulatory collapse

5. PREECLAMPSIA The etiology is unknown believed to be involved: –immune maladaptation –placental ischemia –oxidative stress –genetic susceptibility

6. PREECLAMPSIA Classification of hypertension in pregnancy –Gestational hypertension –Preeclampsia / eclampsia –Chronic hypertension –Preeclampsia superimposed on chronic hypertension

7. PREECLAMPSIA Definition of hypertension –a systolic blood pressure of 140 mmHg or above, –or a diastolic blood pressure of 90mmHg or above, –on two occasions 6 hours apart Abnormal proteinuria –the excretion of 300 mg or more of protein in 24 hours

8. PREECLAMPSIA Criteria for severe preeclampsia –Blood pressure: > 160 mmHg systolic or > 110 mm Hg diastolic –Proteinuria: > 5 g in 24 hours –Persistent and severe cerebral or visual disturbances (headache, scotoma, blurred vision) –Persistent and severe epigastric pain or right upper quadrant pain

9. PREECLAMPSIA Criteria for severe preeclampsia –Pulmonary edema or cyanosis –Oliguria (< 500 mL of urine in 24 hours) –Eclampsia (grand mal seizures) –HELLP syndrome

10. PREECLAMPSIA Screening tests for gestational hypertension routine components of antepartum care trimester early detection of vasoconstriction early detection of altered renal function early detection of altered hemodynamics detection of placental hypoperfusion / ischemia detection of endothelial activation or injury detection of an activated coagulation / fibrinolytic system

11. PREECLAMPSIA 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 fish oil calcium low-dose aspirin

12. PREECLAMPSIA 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

13. PREECLAMPSIA Severe preeclampsia - expectant management –gestational age: not recommended for 34 weeks gestation –hospitalization: tertiary care center –antenatal testing: daily

14. PREECLAMPSIA 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

15. PREECLAMPSIA 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

16. PREECLAMPSIA 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

17. PREECLAMPSIA 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

18. PREECLAMPSIA HELLP syndrome - diagnosis –10% before 27 weeks –20% after 37 weeks –70% between 27 and 37 weeks –slow initial phase with accelerated final phase versus secondary expression of sepsis, ARDS, renal failure

19. PREECLAMPSIA HELLP syndrome –parameters used to diagnose preeclampsia are not reflective of disease severity –target organ systems liver brain kidneys coagulation system –increased maternal and perinatal risk

20. PREECLAMPSIA HELLP syndrome - diagnostic criteria –hemolysis abnormal peripheral smear lactate dehydrogenase > 600 U/L –elevated liver enzymes serum aspartate aminotransferase > 70 U/L lactate dehydrogenase > 600 U/L –low platelets platelet count < 100,000/mm 3

21. PREECLAMPSIA HELLP syndrome - differential diagnosis –acute fatty liver of pregnancy –appendicitis –diabetes insipidus –gallbladder disease –gastroenteritis –glomerulonephritis –hemolytic uremic syndrome –hepatic encephalopathy

22. PREECLAMPSIA HELLP syndrome - differential diagnosis –idiopathic thrombocytopenia –kidney stones –pancreatitis –pyelonephritis –systemic lupus erythematosus –thrombotic thrombocytopenia purpura –viral hepatitis

23. PREECLAMPSIA HELLP syndrome - antepartum management assess and stabilize the maternal condition correct coagulopathy if DIC is present give intravenous magnesium sulfate to prevent seizures provide treatment for severe hypertension to prevent stroke transfer to tertiary center if appropriate if subcapsular hematoma of liver, computed tomography or ultrasound of the abdomen

24. PREECLAMPSIA HELLP syndrome - antepartum management –evaluate fetal well-being non stress test biophysical profile –timing of delivery if > 34 weeks gestation, deliver if < 34 weeks gestation, administer corticosteroids, then deliver in 48 hours

25. PREECLAMPSIA HELLP syndrome - management for cesarean birth –use general anesthesia if platelet count is < 75,000 / mm 3 –transfuse 5 to 10 units of platelets before surgery if platelet count is < 50,000 / mm 3 –leave vesicouterine peritoneum open –install subfascial drain

26. PREECLAMPSIA HELLP syndrome - management for cesarean birth –schedule secondary closure of skin incision or subcutaneous drain –administer postoperative transfusions as needed –perform intensive monitoring for at least 48 hours postpartum –consider dexamethasone (10 mg IV every 12 hours) until postpartum resolution of disease occurs

27. PREECLAMPSIA HELLP syndrome - management of women with a subcapsular liver hematoma –general considerations - blood bank aware for potential need of many units of blood –general or vascular surgeon consultation –avoid direct and indirect manipulation of liver –closely monitor hemodynamic status –management of hematoma depends on whether it is ruptured or not

28. PREECLAMPSIA Eclampsia –occurrence of convulsions or coma unrelated to other associated conditions –all new onset seizures during pregnancy - eclampsia until proven otherwise –incidence: 1 in 500 pregnancies 3% in multiple gestations

29. PREECLAMPSIA Eclampsia –precise cause unknown –theories vasospasm ischemia edema multisystem organ failure

30. PREECLAMPSIA Eclampsia –seizures usually occur without aura –hypertension not severe in 20% –edema absent in 30% –proteinuria absent in 20% –hyperreflexia is not predictive of seizure –headache or visual changes - most common precipitating event

31. PREECLAMPSIA Eclampsia –80% of convulsions occur before or during the delivery –1/3 of cases may be not preventable –atypical less than 20 weeks gestation more than 48 hours postpartum

32. PREECLAMPSIA Eclampsia - risk factors –low socioeconomic status –extremes in childbearing age –African-American –no prenatal care –substance abuse

33. PREECLAMPSIA Eclampsia - management –control convulsions –correction of hypoxia and acidosis –blood pressure control –delivery after maternal stabilization

34. PREECLAMPSIA 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

35. PREECLAMPSIA Eclampsia - magnesium sulfate –side effects: maternal hypotonia respiratory depression cardiac arrest neonatal depression –contraindicated in myasthenia gravis –use with caution in renal insufficiency

36. PREECLAMPSIA 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

37. PREECLAMPSIA Eclampsia - phenytoin –dosage - 1 g loading dose over 1 hour –cardiac monitoring during administration –side effects arrhythmias with rapid administration hepatitis Steven-Johnson syndrome

38. PREECLAMPSIA 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

39. PREECLAMPSIA 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

40. PREECLAMPSIA 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

41. PREECLAMPSIA 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

42. PREECLAMPSIA Eclampsia –delivery is indicated regardless of gestational age –immediate cesarean delivery is not necessary

43. PREECLAMPSIA Eclampsia - radiographic evaluation –should be reserved for women with neurological deficit, recurrent seizures, or atypical presentation –abnormal CT findings - 50% edema, hemorrhage, infarction –cerebral angiography has limited use –90% of EEG evaluations may be abnormal

44. PREECLAMPSIA Eclampsia - management allow patient to have seizure use bite block as needed to prevent maternal injury establish airway administer magnesium sulfate as soon as possible obtain arterial blood gases monitor urine output control hypertension

45. PREECLAMPSIA Eclampsia - management –rebolus with magnesium sulfate if repeat seizure occurs –do not intervene for fetal status while mother is unstable –if seizure continues, paralyze and intubate.

46. PREECLAMPSIA Counseling regarding future pregnancies - HELLP syndrome –information available varies –recurrent risk of preeclampsia: 43% (19%) –recurrent risk of HELLP syndrome: 19-27% (3%) –If HELLP syndrome < 32 weeks recurrent risk of preeclampsia / eclampsia is 61%

47. THANK YOU Sibai BM. Hypertensive disorders in women. 2001. Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol 1998;92:883-9. Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 2003;102:181-92. Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005;105:402-10.