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Hypertension in Pregnancy for Postgraduates Max Brinsmead MB BS PhD January 2016 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 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? How to Measure BP in a Pregnant Woman o Automated machines not recommended o         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?   >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. Differential Diagnosis of Hypertension in Pregnancy  Gestational Hypertension   Preeclampsia   Sustained hypertension after 20w of pregnancy without any other organ involvement. Returns to normal in 3m 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” Systems involved in Preeclampsia  Renal     Hepatic        Eclampsia or stroke Hyperreflexia with sustained clonus Severe headache or visual disturbance Cardiovascular   Thrombocytopenia (<100) Haemolysis DIC CNS   Elevated transaminases (AST or ALT >70) Epigastric or RUQ pain Haematological   Significant proteinuria (>300 mg in 24 hours or P:C > 0.30) S Creat >90 Oliguria Pulmonary oedema Placental   IUGR Abruption 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 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 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  Some rare causes of preeclampsia before 20w  Hydatidiform mole  Fetal triploidy (with or without partial mole)  Severe renal disease  Lupus obstetric syndrome 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 Donors of a kidney have 2.4-fold increased risk of PE but usually not severe 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 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 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?  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 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  Blood tests      Urine 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 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 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 Tests of Fetal Welfare Which Drug is Best for Hypertension in Pregnancy?   The drug that you know best Aldomet   Labetalol   Up to 480 mg/day Nifedipine   Up to 1200 mg/day Oxyprenalol   Up to 2250 mg per day Up to 120 mg/day Prazosin  Up to 15 mg/day Drugs for Hypertension in Pregnancy?  Combination therapy of drugs from different classes is possible e.g.  Aldomet  + Beta blocker + Prazosin Do not use… diuretics – reduce plasma volume  Highly selective beta blokers – cause IUGR  ACE inhibitors – may cause IUFD  Thiazide  Aim for BP 130 -150 systolic and 80 – 100 diastolic Which Drug is Best for Acute Hypertension?  The drug that you know best  IV Hydralazine 5 – 10 mg every 20-30 min   IV Labetalol 20 – 50 mg over 2 min.   Repeat after 15 – 30 min Nifedipine crushed oral 10 mg   or by infusion Repeat after 30 min IV Diazoxide 15 – 45 mg bolus  Repeat after 5 min to a maximum of 300 mg 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 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 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 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 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 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! 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 Postpartum Care  Things may get worse before they get better   Seizure risk is greatest for 48 hrs     Continue MgSO4 infusion for 24 hrs Avoid NSAIDs Treat any BP >150/100   Oliguria for 24 hours is common Use Nifedipine PRN OK to discharge 3d after BP control Follow up weekly to 6w then 3m 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 5066% recurrence risk  Most recover by 12w but these patients are at increased lifetime risk of hypertension and related disease Can Preeclampsia be predicted and prevented?  Identifying the patient at risk  Early pregnancy testing  Prevention strategies  Especially the role of low dose aspirin 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 Patients at risk Prediction of Pre eclampsia  Response to an infusion of angiotensin   Suitable only in a research setting Measure vasoactive proteins in serum PAPP-A, Placental growth factor (PlGF)  Ratio of soluble tyrosine kinase to PIGF has a high negative predictive value (99.3%)   Doppler studies at 12 – 14w   Placental resistance & Uterine artery pulsatility Together these last two can identify 90% of women who will get PE before 34w  With false positive rate of 10% The prevention of pre eclampsia with low dose Aspirin – WHO? History of fetal death or severe IUGR  Patients who previously required delivery for pre eclampsia prior to 34w  Conditions with high risk of pre eclampsia eg Lupus or homozygous for thrombophilia   These patients also require heparin Patients identified by Screening at 12 – 14w (London FMF program)  Also use Ca supplements of 1.5G daily  The prevention of pre eclampsia with low dose Aspirin - Results  Meta analysis suggests that 100 – 150 mg daily started BEFORE 16 w  Reduces risk of early onset pre-eclampsia by 50 – 90%  Less valuable if started after 16w  You need to treat 4-5 women to prevent one FDIU or severe IUGR  RISKS  Does not increase the risk of APH, PPH or fetal intracranial haemoorhage  It is also not teratogenic Other measures to prevent preeclampsia  Anti oxidant supplements (Vitamins C, E)   Folic acid and multivitamins   Requires more RCTs Metformin   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  Unproven and abandonded For the NICE Guideline go to http://pathways.nice.org.uk/pathways/hyperten sion-in-pregnancy Any Questions or Comments? 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