Pre-Eclampsia and Related Disorders

1. Pre-Eclampsia and Related Disorders Critical Care Fellow Teaching Feb 2017

2. Learning Outcomes • Spectrum of disorders • Pathogenesis • Presentation • Reasons to admit to ICU • Treatment • Hypertension • Seizures • Fluid balance

3. Spectrum of Disorders • Pre-eclampsia • Pregnancy induced hypertension with proteinuria • Severe pre-eclampsia • Eclampsia • HELLP syndrome • Haemolysis, elevated liver enzymes and low platelets

4. Preeclampsia • >20/40 gestation • New onset hypertension • SBP >140 +/or • DBP >90 • New onset proteinuria • ≥300mg protein per 24hrs • 2-7% pregnancies • 1.5 maternal deaths per 100,000 deliveries

5. Severe Preeclampsia • CVS/Respiratory • SBP >160 +/or DBP >110 • Pulmonary oedema • Cyanosis • Neurological • Persistent headaches • Visual disturbances • SAH • Raised ICP • Stroke • Renal • Proteinuria ≥2g / 24hrs • PCR >0.2g/mmol • Oliguria <500ml / 24hrs • Creatinine >80 • Hepatic • RUQ or epigastric pain • Raised bilirubin or transaminases • Haematological • Thrombocytopenia • Abnormal clotting studies • Haemolysis

6. Eclampsia • Seizures • Can occur without hypertension or proteinuria • At least 1/3rd occur post delivery • Do still occur >48 hrs post delivery • 0.04-0.1% pregnancies • 1.8% maternal mortality • 7% fetal / neonatal mortality

7. HELLP Syndrome • Severe sub-set of preeclampsia • Predominately hepatic dysfunction (rather than renal and cerebral) • In contrast to preeclampsia pts (Afro-Caribbean and primip’s) are usually white and multip’s • Haemolysis • Elevated Liver enzymes • Low Platelets

8. HELLP Syndrome • RUQ +/or epigastric pain • Nausea • Malaise • Hypertension and proteinuria (usually) • 30% present post partum – may have had no signs of preeclampsia before • Post delivery – get worse for 24-48hrs then gradually improve

9. Severe Complications of HELLP • Severe ascites • Liver haemorrhage • Liver rupture • Liver failure • DIC • Abruption • AKI • Pulmonary oedema • ARDS • Sepsis • Stroke

10. Pathogenesis • Cause(s) not fully understood • Immunological • Genetic (2p, 12q, ?13) • Failure of normal placentation • Endothelial dysfunction • Inflammatory response • Fatty acid metabolism • Coagulation and platelet dysfunction

11. Maternal Risk Factors • <20 or >35 years old • Obesity • Past or family history (4x risk) • Short (<155cm tall) • Pre-existing hypertension • Past history of migraine or renal disease • SLE, antiphospholipid syndrome • Afro-Caribbean origin • Diabetes • Lack of “sperm-mediated partner-specific immune tolerance” • Lower incidence in smokers

12. Fetal Risk Factors • Increased placental mass • Multiple pregnancy (IVF) • Placental hydrops • Molar pregnancy • Genetic factors • Trisomy 13

13. Clinical Features – CVS/Respiratory • Increased SVR – hypertension • Not sympathetically mediated • Very sensitive to vasopressors • Reduced IV volume • Reduced cardiac output • Due to reduced preload and increased afterload (contractility usually ok) • Pulmonary oedema • Leaky capillaries, LV dysfunction, reduced colloid oncotic pressure of pulmonary capillaries • Iatrogenic • Laryngeal oedema

14. Clinical Features - CNS • Cerebral oedema • Raised ICP • Intracranial haemorrhage • Seizures • Cerebral oedema and vasospasm (endothelial dysfunction) • Breakdown of blood brain barrier

15. Clinical Features - Renal • Reduced renal plasma flow and GFR • Glomeruloendotheliosis • Hyperuricaemia • Reduced clearance • Associated with maternal and fetal morbidity and mortality • Rises early in disease • Urine protein/creatinine ratio

16. Clinical Features - Haematological • Thrombocytopenia – DIC • Reduced platelet function

17. Clinical Features - Hepatic • Liver oedema • Hepatocellular necrosis • Hepatic infarcts • Haemorrhage – periportal and subcapsular • Rupture • More common in those with HELLP

18. Why admit to ICU? • Cardiorespiratory failure • Intracranial haemorrhage • Uncontrollable seizures • Renal and hepatic failure • DIC

19. General Management of a Sick Pregnant Woman • Avoid aorto-caval compression • H2 antagonists • Steroids for fetal lung maturation • Early warning score obs – regularly • Serial bloods and urine testing • CTG

20. Specific Management • Delivery of the placenta (and fetus) • Pre-delivery • Control BP • Prevent seizures • Maintain placental perfusion • Prevent complications • Try to avoid premature delivery – major cause of neonatal morbidity and mortality • Post-delivery – largely supportive

21. Delivery • Normal vaginal delivery • Caesarean section • Platelet count • Clotting • Try to avoid GA

22. Hypertension Management • Indicated to prevent stroke, cardiac failure and abruption • SBP >160 +/or DBP >105-110 • Must monitor fetus during treatment • May require cautious IV fluid during treatment as sudden hypotension is possible

23. Pharmacological Management of Hypertension • Hydralazine (IV) – intermittent boluses • Headache, tachycardia, tremor and nausea • Labetalol (IV) – bolus and infusion • Does cross placenta but fetal problems rare • Avoid in asthma and cardiac failure • Nifedipine (oral) • Relaxes uterine smooth muscle – bleeding • Sodium Nitroprusside • Only in hypertensive crisis • GTN (or equivalent) • Good in pulmonary oedema

24. Seizures • Vasospasm and cerebral oedema induced • Warning signs and symptoms include • Visual disturbances, hyper-reflexia, headache • Eclamptic fits are usually short lived and self terminating – can be prolonged • 1/3rd of eclamptic fits occur post partum – can be >48hrs post delivery

25. Seizure Differential Diagnosis • Eclampsia • Epilepsy • Embolism • Clot, air, amniotic fluid • Intra-cerebral pathology • Bleed, thrombus, tumour • LA toxicity • Hyponatraemia

26. Seizure Prophylaxis • Magnesium for 24-48hrs post delivery • Mode of action not totally clear • Calcium antagonism and vasodilatation •  BP •  Renal and uterine blood flow • Blockade / suppression of NMDA receptors

27. Problems with Magnesium • Does needs to be reduced in renal disease • Toxicity • Reference 0.7-1.2 mmol/l • Target 2-3 • Loss of deep tendon reflexes (check upper limb) 3.5-5 • Resp depression >5 • Cardiac arrest >12.5 • Increased PR, QT and QRS at any level over reference range • Tocolytic – slows cervical dilatation • Potentates muscle relaxants • Increased risk of pulmonary oedema • Does cross placenta – floppy baby with resp depression

28. Seizure Treatment • ABC • Magnesium • Diazepam if prolonged • Thiopentone, suxamethonium, opiate, intubate if required • Consider CT head • Standard neuro-critical care management to keep ICP down and CPP up

29. Neuro-Critical Care Management • Treat cause • Bleed • Cerebral oedema • Venous thrombosis • Sedate • 30° head up • PaCO2 4.5-5 kPa • MAP to keep CPP 60-70 mmHg • Don’t obstruct venous drainage • 2 patients – monitor both and liaise with obstetricians – deliver baby when safe to do so

30. Seizure Summary • Identify those at risk – where possible • Prevent – magnesium • Don’t forget differential diagnosis

31. Fluid Balance • Difficult – reduced IV volume and frequently oliguric but high risk of pulmonary oedema • Aggressive fluid loading not encouraged • Maintenance of 75-125ml/hr – all routes • Boluses 250ml crystalloid • CVP for trends – clotting, abnormal ECG • Accept oliguria

32. Pulmonary Oedema • Risk is highest post-delivery – most deaths post partum • Oxygen • Positive pressure ventilation • Invasive or non-invasive • Inotropes • Vasodilators • Diuretics

33. Acute Kidney Injury • Thankfully rare • All patients should have regular creatinine measurements • May require filtration • High chance of full recovery

34. Liver Injury • Supportive • Rupture is a surgical emergency • Otherwise – avoid making it worse

35. Summary • The preeclampsia spectrum are common diagnoses – do not fit into neat categories • Many serious problems occur post delivery • Relapses post delivery do occur – continue monitoring and treating • Managed correctly – good outcome • Full return of normal organ function 6 weeks • Treatment is largely supportive

36. Questions