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Pre-Eclampsia and Eclampsia

Pre-Eclampsia and Eclampsia. Dr Suzy Matts MRCOG Dept Obstetric and Gynaecology George Eliot Hospital. Introduction. Definitions Prevalence Risk Factors Pathogenesis Interventions Prevention treatment. Definition. Hypertension and proteinuria with onset ≥20 weeks

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Pre-Eclampsia and Eclampsia

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  1. Pre-Eclampsia and Eclampsia Dr Suzy Matts MRCOG Dept Obstetric and Gynaecology George Eliot Hospital George Eliot Hospital, Nuneaton

  2. Introduction • Definitions • Prevalence • Risk Factors • Pathogenesis • Interventions • Prevention • treatment George Eliot Hospital, Nuneaton

  3. Definition • Hypertension and proteinuria with onset ≥20 weeks • Oedema from classical definition dropped as not discriminating clinically • Diastolic ≥90mmHg on 2 occasions 4-6 hours apart OR ≥110mmHg on one occasion • Proteinuria >300mg/24 hours • Symptoms • Differentiation from PIH/renal disease George Eliot Hospital, Nuneaton

  4. Hypertensive disorders George Eliot Hospital, Nuneaton

  5. Incidence • 2-3% pregnancies • 5-7% primips • 1.8% PET will develop eclampsia (from Collaborative Eclampsia Trial = 49/ 100000) • Rates eclampsia 26.8/100 000 maternities (UKOSS reporting system 2003-5) • Worldwide 1.5-8 million develop PET with 150 000 deaths George Eliot Hospital, Nuneaton

  6. Importance • Important cause of maternal and fetal death • 2nd most common cause maternal death over a number of years • 15 deaths 1997-9 • 14 deaths 2000-2 • 18 deaths 2003-5 (=8.5/million maternities) • High rates of substandard care (72% 2003-5) George Eliot Hospital, Nuneaton

  7. Importance • Maternal morbidity • Blindness • Neurological • renal • Fetal death • Abruption, hypoxia, IUGR • Fetal morbidity • Prematurity (PET is cause of >40% iatrogenic preterm dels) with risks respiratory and neurodevelopmental complications (inc.learning difficulty/IQ in up to 60%) George Eliot Hospital, Nuneaton

  8. Causes of death George Eliot Hospital, Nuneaton

  9. Pre-Eclampsia and EclampsiaDeaths 2003-5 • 18 women • 10 died of cerebral haemorrhage • 2 died of cerebral infarction (one with 2ry haemorrhage) • 2 from multiorgan failure (inc ARDS) • 1 from massive liver infarction • 3 from other causes • Rate of death overall unchanged from previous report George Eliot Hospital, Nuneaton

  10. Primiparous First pregnancy with new partner Family history (1 in 3 risk if mother had PET) Twins/multiples Pregestational Diabetes Essential hypertension Renal disease SLE Antiphospholipid syndrome Thrombophilias Age >40 Obesity Risk Factors:-Pre-Eclampsia George Eliot Hospital, Nuneaton

  11. Pathophysiology • “The disease of theories” • Pregnancy specific syndrome • Placenta has a central role to play • Reduced placental perfusion • Inadequate vascular remodelling at ~16 wks • Genetic component in some women tho’ not in others • No candidate genes or consistent results George Eliot Hospital, Nuneaton

  12. Pathophysiology of PET George Eliot Hospital, Nuneaton

  13. 2 stage process • Inadequate implantation • Poor remodelling • Cytokines produced + growth factors • placental apoptosis/necrosis • Shedding of microparticles into circulation • Markers seen preceding PET • Inflammation and endotheial activation STAGE 1:Reduced placental perfusion STAGE 2: Maternal syndrome (multisystem disorder) George Eliot Hospital, Nuneaton

  14. Oxidative stress • Evidence includes superoxide dysmutase in placenta and maternal blood in PET Maternal constitutional factors eg obesity, genetic, diabetes, environment, diet Stage 1: placental perfusion OXIDATIVE STRESS Stage 2: Maternal syndrome (activation of maternal endothelium) George Eliot Hospital, Nuneaton

  15. Angiogenic Factors • e.g. sFlt-1 or soluble endglin coreceptor-inhibit growth factors in placenta and vasculature Maternal constitutional factors eg obesity, genetic, diabetes, environment, diet Stage 1: placental perfusion ANGIOGENIC FACTORS Stage 2: Maternal syndrome (activation of maternal endothelium) George Eliot Hospital, Nuneaton

  16. Prevention of PET: Aspirin • Several small trials suggested reduction in rates PET with low dose aspirin therapy • Large multicentre trial (CLASP) in 9364 women did not demonstrate benefit for wholescale prophylaxis for low risk women • Trend towards reduction in likelihood to preterm delivery • No significant increased risk of haemorrhages • No statistically significant effect on stillbirths/ neonatal deaths • Non significant (12%) reduction in incidence PET Lancet 1994; 343: 619-629 George Eliot Hospital, Nuneaton

  17. CLASP • Trial suggested only benefits in women at high risk of severe early onset IUGR ? How to identify • Benefits thus suggested in women with previous severe early onset PET and IUGR • ?relationships to APLS (not investigated in original trial) George Eliot Hospital, Nuneaton

  18. Prevention: Aspirin • More recent study showed aspirin treatment produced at RR of 0.9 (95% CI 0.84-0.97) for PET • Moderate but consistent reductions in PET, preterm delivery and serious outcomes Lancet 2007 George Eliot Hospital, Nuneaton

  19. Prevention: Calcium • Calcium levels lower in women with PET compared to ‘normal’ pregnancy • Australian Randomised Study in 456 singleton nullips from <24/40 showed reduction in risk PET with 1.8g calcium/day compared to placebo • RR 0.44 95% CI 0.21-0.90 Aus NZ J Obstet Gynaecol 1999; 39: 12-18. George Eliot Hospital, Nuneaton

  20. Prevention: Calcium • Calcium for Eclampsia Prevention Study (CPEP) Am J Obstet Gynecol 1997; 177: 1003-10 • 4589 US women in multicentre trial • All nullips • Analysis of risk factors for development of subsequent PET did not show any benefit from Ca++ supplementation George Eliot Hospital, Nuneaton

  21. Prevention: Calcium • Cochrane Review Cochrane Database 2000 (3), OUS. • 9 studies, all good quality • Ca++ dose > 1g/day • Modest reduction in risk PET for all women (RR 0.72, 95% CI 0.6-0.86) • Greatest effect where highest risk- RR 0.22, 0.11-0.43 and low dietary intake (0.32, 0.21-0.49) • No effect on preterm delivery • Smaller effects seen for hypertension • Ca++ appears of benefit for women at high risk of developing PET • Also women from communities with low dietary intake • Optimum dosage requires further evaluation George Eliot Hospital, Nuneaton

  22. Prevention: Antioxidants • Vitamin C 1000mg and Vit E 400 IU/day • 58% reduction in PET in treated group Chappell et al, Lancet 1999 354: 810-5 • A number of trials ongoing globally • All using above dosages • 3 reported so far-NO difference in rates treatment vs placebo. George Eliot Hospital, Nuneaton

  23. Diagnosis: Pre-Eclampsia • Classic triad • Hypertension 140/90 • Proteinuria >300mg in 24 hours (RCOG) • Oedema (least reliable) • BP rise should be from booking >30/15 • Proteinuria and raised BP x 2 occasions 6 hrs apart (or once if DBP ≥110 and heavy proteinuria >2+ (=1g/24h)) George Eliot Hospital, Nuneaton

  24. Mild PET • Classically asymptomatic • BP 140/90 (ish) • Maybe trace-+ proteinuria • Often incidental finding at CMW clinic attendance George Eliot Hospital, Nuneaton

  25. PET-Investigations • FBC- platelet count • U+E signs renal dysfunction (late) • Urate hyperuricaemia ( early ) • LFTs elevated transaminases • Clotting XXXX (not routinely if plts>100) • MSU to exclude UTI as cause of protein George Eliot Hospital, Nuneaton

  26. PET • Fetal assessment • Clinical • USS for growth • CTGs • ?cervical assessment (depending on gestation) George Eliot Hospital, Nuneaton

  27. Monitoring • Monitor BP • CMW • Day assessment or Triage Unit • Monitor bloods • Weekly or twice weekly (depends on sitn) • Monitor fetus • CTG • Serial USS George Eliot Hospital, Nuneaton

  28. Definitive treatment • Deliver when • BP/protein or clinical condition deteriorates so become moderate or severe PET • Reaches 41 weeks and no change in condition • Fetal condition mandates delivery even if maternal condition stable George Eliot Hospital, Nuneaton

  29. SYSTOLIC 160-180 DIASTOLIC >110 CNS Headache Visual disturbances Disorientation/ irritability Hyperreflexia clonus Hepatic Abnormal LFTs, dysfunction RUQ pain Epigastric pain Renal Elevated creatnine, urea, urate Oliguria Heavy proteinuria >5g in 24 hrs Haemtological Thrombocytopaenia haemolysis Severe pre-eclampsia George Eliot Hospital, Nuneaton

  30. Eyes Arteriolar spasm Retinal haemorrhages Blindness Scotoma Papilloedema CNS Seizures Encephalopathy Cerebral haemorrhages CVA Respiratory Pulmonary oedema ARDS Liver Subcapsular haemorrhages Liver rupture Kidneys Acute renal failure Fetoplacental Unit IUGR Abruption Fetal compromise Fetal death Haemotological DIC haemolysis Multisystem disease George Eliot Hospital, Nuneaton

  31. Symptoms • Headache (BP) • Flashing lights (lightning) (cerebral oedema) • Epigastric pain (stretching of liver capsule) • Oedema (albumin/BP) • Asymptomatic George Eliot Hospital, Nuneaton

  32. Management of severe pre-eclampsia • Immediate admission to hospital • High dependency care/LW-QUIET • Invasive monitoring • NICU for baby if early gestation • Senior multidisciplinary involvement early-obs and anaesthetics George Eliot Hospital, Nuneaton

  33. Aims of treatment • Aims • Prevent seizures • Control hypertension (to prevent cerebral haemorrhage) • Deliver safely (stabilise, +/- IUT, +/- steroids) George Eliot Hospital, Nuneaton

  34. Maternal Assessment • BP-check every 15 minutes • Urine output-hourly • Urinary protein dipstix • Strict fluid balance chart • Bloods • U+E, urea, creatnine, urate • FBC esp. platelets (G+S) • LFTs • Deep tendon reflexes and presence of clonus • CTG George Eliot Hospital, Nuneaton

  35. Control blood pressure • Antihypertensives – aim for diastolic 85-95 • IV hydralazine (5mg every 15 minutes to acutely control BP) • IV labetolol (Not good if asthmatic or already signs of pulmonary oedema-first line in many places now) • Oral nifedipine 10mg NOT SUBLINGUAL • Methyldopa TOO SLOW ONSET (24-48 hours) for use in acute situation • Titrate IV antihypertensive vs. BP then infusion George Eliot Hospital, Nuneaton

  36. KEY POINTS: Hypertension Systolic blood pressure of 160 mm/Hg or more = anti-hypertensive treatment. (irrespective of diastolic) Consideration starting treatment at lower pressures if the overall clinical picture suggests likely rapid deterioration with anticipation of severe hypertension. George Eliot Hospital, Nuneaton

  37. Prevent Fits • Magnesium sulphate • All severe and moderate PET (MAGPIE) • 4g IV over 15 minutes • Then infusion 1g/ hour • Monitor reflexes (present) urine OP (>30ml/hr) and respiratory rate (>12/minute) • Slows neuromuscular conduction and decreases CNS irritability • Best anticonvulsant in these circumstances AND IN ECLAMPSIA • No effect on BP • Tell anaesthetist if GA as potentiates effects of muscle relaxants George Eliot Hospital, Nuneaton

  38. If urine OP OK then likely not to accumulate (85% renal excretion) If urine output falls, reduce dose to 0.5g/hour If signs toxicity, stop Antidote = Calcium gluconate 1g IV over 3 minutes Magnesium levels Therapeutic 2-4 mmol/l Warmth, flushing, slurred speech 3.8-5mmol/l Loss of patellar reflexes >5 mmol/l Respiratory depression >6 mmol/l Respiratory arrest 6.3-7mmol/l Cardiac arrest, asystole >12 mmol/l Magnesium toxicity George Eliot Hospital, Nuneaton

  39. MAGPIE • 10141 women-99% received allocated treatment • 24% of women with MgSO4 reported side-effects compared to 5% of women on placebo • MgSO4 produced 58% reduced risk of eclampsia (0.8% cf. 1.9%)-across all categories of PET • Maternal mortality lower as well RR 0.55, CI 0.26-1.14 • Only improvement in maternofetal morbidity was reduced risk of abruption (0.67, 99% CI 0.45-0.89) • No substantial harmful risks to mother or fetus Lancet 2002; 359: 1877-90. George Eliot Hospital, Nuneaton

  40. MAGPIE Lancet 2002; 359: 1877-90. George Eliot Hospital, Nuneaton

  41. Deliver Baby • If severe PET, should NOT transfer • Ensure SCBU aware if baby premature • Give antenatal steroids if time but usually, if require IV therapy, delivery is indicated once stabilised • If cervix favourable and patient >36 weeks, consider short trial IOL • If cervix unfavourable and/or <36 weeks, deliver by LSCS • Anaesthesia epidural vs. general George Eliot Hospital, Nuneaton

  42. DELIVERY: Key Points 1 Risk of sharp rise of BP on intubation This may be obtunded by large dose alfentanyl or similar Need experienced and senior anaesthetist to give GA in these circumstances George Eliot Hospital, Nuneaton

  43. DELIVERY: Key Points 2 Syntometrine should not be given for the active management of the third stage if the mother is hypertensive, or if her blood pressure has not been checked. (ergometrine causes vasospasm and a sharp rise in BP which may precipitate hypertensive crisis, fits or cerebral haemorrhage) George Eliot Hospital, Nuneaton

  44. Eclampsia • Occurrence of fits • 44% postpartum • 38% antenatal) • ALWAYS GRAND MAL • Due usually to cerebral vasospasm • Do not try to shorten initial convulsion (self-limiting) • Prevent maternal injury • Maintain oxygenation • Prevent aspiration • ABC… George Eliot Hospital, Nuneaton

  45. Eclampsia • Beware known epileptics • If BP normal, no protein, typical for their type of fit-may be epilepsy BUT any fit must be considered as eclampsia until proven otherwise especially of BP slightly up etc • Any FOCAL fit is not eclampsia • Consider SOL eg cerebral bleed/infarction due to severe PET • Arrange head CT urgently George Eliot Hospital, Nuneaton

  46. Collaborative Eclampsia Trial • Multicentre international trial Lancet 1995; 345: 1455-63 • 1687 women • Comparisons: • MgSO4 vs. diazepam • 52% lower risk recurrent convulsions with MgSO4 • MgSO4 vs. phenytoin • 67% lower risk recurrent convulsions with MgSO4 • Maternal mortality nonsignificantly lower in MgSO4 • Less risk of pneumonia, ventilation, ITU with Magnesium • Babies less likely to be intubated and go to SCBU George Eliot Hospital, Nuneaton

  47. Eclampsia • Treatment is IV magnesium sulphate-4g loading then 1g/hr • If recurrent fits or fit already on MgSO4, then further 2g IV bolus/increase infusion to 1.5g/hr • If fits persist, check magnesium levels, contact anaesthetists, consider CT, consider intubation and ventilation • If antenatal, stabilise and Deliver George Eliot Hospital, Nuneaton

  48. Following Delivery • Watch closely on HDU/LW until diuresis and condition improving • Anticipate possible worsening or seizures in first 18-24 hours • Continue MgSO4 for 24 hours and then review • Do not need to taper off MgSO4 • Do not feed within 12 hours as significant risk ileus-sips H2O only until next morning then review for bowel sounds George Eliot Hospital, Nuneaton

  49. Postnatal care • Watch closely on HDU/LW until diuresis and condition improving • Anticipate possible worsening or seizures in first 18-24 hours • Continue MgSO4 for 24 hours and then review • Do not need to taper off MgSO4 • Do not feed within 12 hours as significant riskileus-sips H2O only until next morning then review for bowel sounds George Eliot Hospital, Nuneaton

  50. Postnatal Care • Managing the postnatal pre-eclamptic poses particular challenges • Hypertension • Fits • Fluid management • GI management • Disease progression George Eliot Hospital, Nuneaton

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