Hypertension in Pregnancy for Postgraduates

1. Hypertension in Pregnancyfor Postgraduates Max Brinsmead PhD FRANZCOG April 2013

2. This talk • How to measure BP • When is a pregnant woman hypertensive • What is the Differential Diagnosis • What tests are required and how do you interpret them • Tests for proteinuria • Risk factors for pre-eclampsia • Pathophysiology of pre eclampsia • How to manage the hypertensive gravida • Which is the best drug to lower BP

3. This talk(2) • Who should be delivered? How & Where • Best practice intrapartum care • Who requires an anticonvulsant? • What is the best drug for Eclampsia? • Best practice postpartum care • Best practice anaesthetic care • Prognosis after pre-eclampsia • Can pre-eclampsia be predicted? • Can pre-eclampsia be prevented?

4. How to Measure BP in a Pregnant Woman • Automated machines not recommended • Unless calibrated against a mercury sphygmomanometer in the individual patient • Appropriate sized cuff • Seated for 2 - 3 minutes with feet supported • Both arms first visit • Palpate systolic and go 20 mm higher • Deflate slowly 2 mm every sec • Use Korotkoff 5 (or 4 if 5 absent) for diastolic • Repeated measures may be required • Ambulatory monitoring useful for White Coat Hypertension

5. When is a Pregnant Woman Hypertensive? • >140/90 on >one occasion • (Rise of >30 systolic or >15 diastolic) • Knowledge of prior BP very important • Not in itself diagnostic – look for other problems • Severe hypertension is >169 systolic and or diastolic >109 • Requires admission and urgent Rx • However, the diagnosis is more important than the actual level of BP.

6. Differential Diagnosis of Hypertension in Pregnancy • Gestational Hypertension • Sustained hypertension after 20w of pregnancy without any other organ involvement. Returns to normal in 3m • Preeclampsia • Sustained hypertension after 20w of pregnancy with evidence of other organ involvement. Returns to normal in 3m • Chronic Hypertension • Hypertensive before 20w. 95% is Essential Hypertension Includes “White Coat Hypertension”

7. Systems involved in Preeclampsia • Renal • Significant proteinuria (>300 mg in 24 hours or P:C > 0.30) • S Creat >90 • Oliguria • Hepatic • Elevated transaminases (AST or ALT >70) • Epigastric or RUQ pain • Haematological • Thrombocytopenia (<100) • Haemolysis • DIC • CNS • Eclampsia or stroke • Hyperreflexia with sustained clonus • Severe headache or visual disturbance • Cardiovascular • Pulmonary oedema • Placental • IUGR • Abruption

8. Please note • I have not used the words “Pregnancy induced Hypertension” or PIH • No mention is made of oedema • Proteinuria is the most common manifestation of “other system involvement” and some method of assessment is critical to good obstetric care • Evidence for other organ involvement in Pre eclampsia is a mix of symptoms, signs and tests

9. Tests of Proteinuria • The screening test is by dipstick • Have a sensitivity >90% using ≥ 1+ • But correlate poorly with high protein loss • And false negative rates up to 20% • Will miss >300 mg/24 hours in up to 1:8 patients • And the test strips spoil quickly in humidity • Boiling urine is sensitive and quantifiable • But messy and disliked by midwives • 24 hour collection and quantification by lab • Is the gold standard • But labour intensive and slow • The protein:creatinine ratio on a spot sample is a good compromise

10. Proteinuria in Practice • Significant proteinuria occurs when... • There is ≥ 2+ on dipstick • Trace or 1+ should be regarded as equivocal • The 24 hour urine collection is > 300 mg • The spot urine protein:creatinine ratio is ≥ 30 mg/mmol • There is > “cloud” on boiled urine • When significant proteinuria has been detected there is little point in repeating the measure

11. Some rare causes of preeclampsia before 20w Hydatidiform mole Fetal triploidy (with or without partial mole) Severe renal disease Lupus obstetric syndrome

12. Renal Disease in Pregnancy • Responsible for about 5% of chronic hypertension • Causes include: • chronic or recurrent infection • glomerulonephritis • renal artery stenosis • Must be assessed by creatinine clearance (CC) which doubles in normal pregnancy • When CC falls below 50% the prognosis is very bad • Monitoring for superimposed pre eclampsia can be difficult if there is chronic proteinuria

13. Some rare causes of hypertension • Coarctation of the aorta • Sometimes the clue is to measure BP in both arms • There is a systolic murmur that can be heard in the back • Phaeochromocytoma • Paroxysms of symptomatic hypertension • The clue to diagnosis is to think of it • Associated with high levels of catecholamines • Hyperaldosteronism • Also known as Conn’s disease

14. Pathophysiology of Pre eclampsia • Placental tissue • In healthy pregnancies cytotrophoblast infiltrates the decidual portion of the uterine spiral arteries • In order to increase maternal blood flow to the placenta • In patients destined to develop pre eclampsia this fails to occur • This results in placental hypoperfusion • These changes occur at <16 weeks gestation but the pre eclampsia may not be manifest until much later in the pregnancy

15. Pathophysiology of Pre eclampsia • Hypoperfusion of the Placenta • Becomes worse as pregnancy progresses • The abnormal uterine vasculature is unable to accommodate the normal rise in blood flow to the fetus/placenta that occurs with increasing gestational age. • Late placental changes consistent with ischemia include atherosis (lipid-laden cells in the wall arterioles), fibrinoid necrosis, thrombosis, sclerotic narrowing of arterioles, and placental infarction

16. Pathophysiology WHY? • An ‘immunolgical’ response to pregnancy ---in ‘at risk’ or predisposed women • A response to a conceptus whose genetic material is 50% foreign (from the father) • A failure of ‘Blocking Antibody’ • This disease is still a mystery

17. Pathophysiology WHAT? • Contracted intravascular volume of mother • In reality a failure to increase plasma volume • ↑Sensitivity to pressure agents • Leaky Capillaries • Reduced oncotic pressure • In part due to low serum albumen • Poor placental reserve • A fetus at risk of hypoxia and death

18. Pathophysiology WHAT? • Hypertension/ Proteinuria/ oedema • Low platelets Consumption • Raised urate Cell (DNA) death • Raised Haematocrit Reduced plasma volume • Haemolysis • Abnormal LFT’s • Abnormal clotting Widespread DIC

19. Tests for the Hypertensive Gravida • Blood tests • FBC - look at HB, Haematocrit and Platelets • UEC - look at Creatinine Should be < 0.07 (or 70) • URATE - equivalent to weeks gestation • Liver enzymes – AST & ALT should be <70. Ignore ALP • Urine Tests • UMCS - exclude UTI and look for casts • Protein:Creatinine ratio from spot test >30 significant • 24 hr protein excretion >300 mg/day significant • Assess fetal welfare by CTG & Scan for AFI and UA Dopplers

20. Frequency of Testing

21. Management of Hypertensive Gravida • Hospitalise if pre-eclamptic • Discharge if “just BP” • Bed rest only when there is proteinuria • Control BP to protect mother from severe hypertension • Role of antihypertensive agents for mild & moderate chronic hypertension is controversial • Delivery will cure pre eclampsia & gestational hypertension • Remember thromboprophylaxis

22. Tests of Fetal Welfare

23. Which Drug is Best for Hypertension in Pregnancy? The drug that you know best Aldomet Up to 2250 mg per day Labetalol Up to 1200 mg/day Oxyprenalol Up to 480 mg/day Nifedipine Up to 120 mg/day Prazosin Up to 15 mg/day

24. Drugs for Hypertension in Pregnancy? Combination therapy of drugs from different classes is possible e.g. Aldomet + Beta blocker + Prazosin Do not use… Thiazide diuretics – reduce plasma volume Highly selective beta blokers – cause IUGR ACE inhibitors – may cause IUFD Aim for BP 130 -150 systolic and 80 – 100 diastolic

25. Which Drug is Best for Acute Hypertension? • The drug that you know best • IV Hydralazine 5 – 10 mg every 20-30 min • or by infusion • IV Labetalol 20 – 50 mg over 2 min. • Repeat after 15 – 30 min • Nifedipine crushed oral 10 mg • Repeat after 30 min • IV Diazoxide 15 – 45 mg bolus • Repeat after 5 min to a maximum of 300 mg

26. Which Drug is Best for Eclampsia? • First aid is more important than drugs • Protect from injury • Secure an airway • Administer oxygen • Then secure IV access • IV MgSO4 4G over 10 – 15 min • Then 1 -2 G/hour by infusion • If seizure recurs then give another 2 – 4 G bolus • IV Diazepam only for status eclampticus • Monitor urine output, respirations, O2 saturation and DTJ’s

27. Who Needs Fluid Expansion? • If there is severe proteinuria and oliguria • Then give 500 – 1000 ml cautiously • Injudicious use carries a risk of pulmonary oedema and adult RDS • Pre load prior to epidural or spinal • Consult with anaesthetist • Use colloids rather than crystalloids • Sometimes required if BP drops suddenly • Sometimes occurs with Diazoxide/Hydralazine • CTG monitoring desirable • Abruption requires prompt resuscitation • Often requires blood • Watch urine output and/or JVP

28. Who Requires Delivery? • Pre eclampsia >36 completed weeks • Uncontrollable hypertension • Deteriorating renal, hepatic or haematologic state • For GA >32w and good neonatal facilities delay only long enough to give steroids • Eclampsia or imminently eclamptic • Fetus is compromised • APH - abruption

29. Induction of Labour vs Expectant Management for Gestational Hypertension Koopmans et al Lancet 2009 • The HYPITAT study • A multicentre RCT of 756 women in Netherlands • Were 36 – 41 weeks with a diagnosis of mild pre eclampsia or gestational hypertension • Of the women randomised to induction of labour 31% had a poor outcome vs 44% for observation (RR=0.71, CI 0.59-0.86, p<0.001) • Poor outcomes included eclampsia, HELLP, severe pre eclampsia and PPH • No greater risk of Caesarean or neonatal morbidity • Active management is also more cost effective

30. How to Deliver • Deliver vaginally if >37w and Cx is favourable • or can be ripened • Caesarean only if the above not met • Elective CS usually at gestations <35w • Inappropriate attempts at delivery when it is not indicated is an invitation to CS (and more CS) • Deliver in an environment that can cope with a severe multisystem disease • Don’t overlook patient’s and family’s psychological needs

31. Intrapartum Care • Assess convulsive risk and consider prophylactic MgSO4 • Control BP with an epidural or IV Hydralazine • Careful fluid balance • Monitor the fetus • Avoid ergometrine • SVD is not a sin!

32. Anaesthetic Implications • Epidural good for both vaginal & abdominal delivery • Spinal + Vasopressin also okay • Spinal plus epidural for a few cases • Low dose aspirin okay for epidural • GA for acute fetal compromise or low platelets • <50, and 50 – 75 is a grey zone • Watch for hypertension during GA intubation • Use antacid and lateral tilt • Cautious use of oxytocin boluses

33. Postpartum Care • Things may get worse before they get better • Oliguria for 24 hours is common • Seizure risk is greatest for 48 hrs • Continue MgSO4 infusion for 24 hrs • Avoid NSAIDs • Treat any BP >150/100 • Use Nifedipine PRN • OK to discharge 3d after BP control • Follow up weekly to 6w then 3m

34. The Prognosis after Pre eclampsia • Mild pre eclampsia near term has a low recurrence risk • Unless there is a new partner or a long gap to the next pregnancy • Severe pre eclampsia prior to 34w has a 50- 66% recurrence risk • Most recover by 12w but these patients are at increased lifetime risk of hypertension and related disease

35. Can Preeclampsia be predicted and prevented? Identifying the patient at risk Early pregnancy testing Prevention strategies Especially the role of low dose aspirin

36. Risk factors for severe pre eclampsia • Previous pre eclampsia at <35w • Renal disease • Thombophilias • Autoimmune disease e.g. SLE • Diabetes • Multiple pregnancy • Severe alloimmunisation • Family history of pre eclampsia • Obesity • Increasing maternal age

37. Patients at risk

38. Prediction of Pre eclampsia • Risk factors alone are insensitive and non specific • Tests of plasma volume • BP response to an infusion of angiotensin • Suitable only in a research setting • Measure vasoactive proteins in serum • Soluble vascular endothelial or placental growth factors • Uterine artery Doppler wave forms • Look for bilateral notching or high pulsatility index at 20w • “Almost 100% sensitive” for early onset disease (<32w) • Start aspirin 100 mg and see frequently

39. The prevention of pre eclampsiawith low dose Aspirin • History of fetal death or severe IUGR • Patients who required delivery for pre eclampsia prior to 34w • You need to treat 4-5 to prevent one FDIU or severe IUGR • Does not increase the risk of APH or PPH • Conditions with high risk of pre eclampsia eg Lupus or homozygous for thrombophilia • These patients also require heparin • Also give Ca supplements 1.5 G/day

40. Measures to prevent preeclampsia that are not effective Anti oxidant supplements (Vitamins C, E) Increase the risk of stillbirth and IUGR Folic acid and multivitamins Requires RCTs Abdominal decompression Unproven