Hypertension in Pregnancy for Postgraduates Max Brinsmead MB

Hypertension in Pregnancy for Postgraduates Max Brinsmead MB BS Ph. D January 2016

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

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

How to Measure BP in a Pregnant Woman o Automated machines not recommended o l l l l 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

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

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

Systems involved in Preeclampsia l Renal l l Hepatic l l l l Eclampsia or stroke Hyperreflexia with sustained clonus Severe headache or visual disturbance Cardiovascular l l Thrombocytopenia (<100) Haemolysis DIC CNS l l Elevated transaminases (AST or ALT >70) Epigastric or RUQ pain Haematological l l Significant proteinuria (>300 mg in 24 hours or P: C > 0. 30) S Creat >90 Oliguria Pulmonary oedema Placental l l IUGR Abruption

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

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

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

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

Renal Disease in Pregnancy l Responsible for about 5% of chronic hypertension l Causes include: chronic or recurrent infection l glomerulonephritis l renal artery stenosis l l l 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 Donors of a kidney have 2. 4 -fold increased risk of PE but usually not severe

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

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

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

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

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

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

Tests for the Hypertensive Gravida l Blood tests l l l Urine Tests l l 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 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

Frequency of Testing

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

Tests of Fetal Welfare

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

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

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

Which Drug is Best for Eclampsia? l First aid is more important than drugs Protect from injury l Secure an airway l Administer oxygen l Then secure IV access l l l IV Mg. SO 4 4 G 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, O 2 saturation and DTJ’s

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

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

Induction of Labour vs Expectant Management for Gestational Hypertension Koopmans et al Lancet 2009 l l l l 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

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

Intrapartum Care Assess convulsive risk and consider prophylactic Mg. SO 4 l Control BP with an epidural or IV Hydralazine l Careful fluid balance l Monitor the fetus l Avoid ergometrine l SVD is not a sin! l

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

Postpartum Care l Things may get worse before they get better l l Seizure risk is greatest for 48 hrs l l Continue Mg. SO 4 infusion for 24 hrs Avoid NSAIDs Treat any BP >150/100 l l Oliguria for 24 hours is common Use Nifedipine PRN OK to discharge 3 d after BP control Follow up weekly to 6 w then 3 m

The Prognosis after Pre eclampsia l Mild pre eclampsia near term has a low recurrence risk l Unless there is a new partner or a long gap to the next pregnancy l Severe pre eclampsia prior to 34 w has a 5066% recurrence risk l Most recover by 12 w but these patients are at increased lifetime risk of hypertension and related disease

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

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

Patients at risk

Prediction of Pre eclampsia l Response to an infusion of angiotensin l l Suitable only in a research setting Measure vasoactive proteins in serum PAPP-A, Placental growth factor (Pl. GF) l Ratio of soluble tyrosine kinase to PIGF has a high negative predictive value (99. 3%) l l Doppler studies at 12 – 14 w l l Placental resistance & Uterine artery pulsatility Together these last two can identify 90% of women who will get PE before 34 w l With false positive rate of 10%

The prevention of pre eclampsia with low dose Aspirin – WHO? History of fetal death or severe IUGR l Patients who previously required delivery for pre eclampsia prior to 34 w l Conditions with high risk of pre eclampsia eg Lupus or homozygous for thrombophilia l l These patients also require heparin Patients identified by Screening at 12 – 14 w (London FMF program) l Also use Ca supplements of 1. 5 G daily l

The prevention of pre eclampsia with low dose Aspirin - Results l Meta analysis suggests that 100 – 150 mg daily started BEFORE 16 w l Reduces risk of early onset pre-eclampsia by 50 – 90% l Less valuable if started after 16 w l You need to treat 4 -5 women to prevent one FDIU or severe IUGR l RISKS l Does not increase the risk of APH, PPH or fetal intracranial haemoorhage l It is also not teratogenic

Other measures to prevent preeclampsia l Anti oxidant supplements (Vitamins C, E) l l Folic acid and multivitamins l l Requires more RCTs Metformin l l Increase the risk of stillbirth and IUGR. Trials stopped Improves uteroplacental circulation and reduces the rate of pre eclampsia and pre term birth for PCO patients who take it in early pregnancy. Needs study in a wider group of patients Abdominal decompression l Unproven and abandonded

For the NICE Guideline go to http: //pathways. nice. org. uk/pathways/hyperten sion-in-pregnancy

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