1. Hypertensive Disorders of Pregnancy Family Medicine Specialist Program CME

2. Case A 32 year-old G2P1 woman presents for her routine ante-natal visit at 32 weeks’ gestation. Her BP is 140/90. Throughout her pregnancy to date her BP has ranged from 115/75 to 130/85. Her weight is 105 kg. What steps do you perform as part of your initial investigation?

3. Case - continued Repeated blood pressures over the next three hours range from 140/90 to 155/95. What is your management plan?

4. Objectives Describe the classification of hypertension in pregnancy. Discuss the appropriate monitoring and management of hypertension in pregnancy and pre-eclampsia. Discuss how to determine the appropriate medication according to the condition of the woman. Describe a Quality Improvement project with regards to patients presenting with hypertension in pregnancy.

5. Classification of Hypertension 1.Pre-existing hypertension – With co-morbid conditions – With Pre-eclampsia Resistant hypertension New or worsening proeinuria > 1 adverse conditions(s) 2.Gestational hypertension – With co-morbid conditions – With Pre-eclampsia New or worsening proteinuria > 1 adverse conditions(s)

6. Determining Blood Pressure Sitting position with arm at heart level Appropriate size BP cuff Accurate mercury sphygmomanometer Repeat measurements in > 4 hour intervals unless very high

7. Definitions Hypertension Diastolic BP of >90 mm Hg on 2 measurements > 5 minutes apart after a period of 10 minutes rest Diastolic BP of > 110 mm Hg on a single measurement

8. Hypertension - Definition Pre-existing hypertension – Hypertension < 20 weeks gestation Gestational hypertension – Onset of hypertension > 20 weeks gestation (includes preeclampsia)

9. Preeclampsia- Definition Hypertensive disorder of pregnancy – With pre-existing hypertension this means: resistant hypertension New/worsening proteinuria One or more adverse conditions – With gestational hypertension New-onset proteinuria One or more adverse conditions

10. Severe Preeclampsia - Definition Onset before 34 weeks gestation Associated with heavy proteinuria – 3 – 5 gms per day With onset of one or more adverse conditions

11. Definition Proteinuria – Indicates glomerular dysfunction – Urine protein > +2 on dipstick – Urine protein > 200 mg/L on 24 hour collection or urine protein/creatinine ratio > 0.03 on spot check – 24 hour urine analysis should be considered if urine protein > +1 on dipstick Edema is NOT part of the definition

12. Preeclampsia Adverse Conditions (1) Vascular/Pulmonary – BP sBP > 160 mm Hg dBP > 110 mm Hg – Pulmonary edema – Chest pain – Shortness of breath (dyspnea)

13. Preeclampsia Adverse Conditions (2) Renal – Oligouria – Elevated serum creatinine – Serum albumin <20 g/L Hepatic – Abdominal/epigastric/right upper quadrant pain – Severe nausea or vomiting – Elevated liver enzymes – AST, ALT, LDH

14. Preeclampsia Adverse Conditions (3) Central Nervous System – New or unusual headache – Seizures (eclampsia) – Visual disturbances HELLP Syndrome – Hemolysis – Elevated liver enzymes (AST, ALT, LDH) – Low platelet count

15. Preeclampsia Adverse Conditions (4) Hematological – Decreased platelets <100,000 – Disseminated intravascular coagulopathy (DIC)

16. Hypertension & Fetal consequences Intrauterine growth restriction (IUGR) Oligohydramnios Placental abruption Prematurity Fetal compromise Intrauterine fetal death

17. Incidence 10% of all pregnancies complicated by hypertension –one third of these will have proteinuria majority of preeclampsia in nulliparous patients –2 to 5 % –Increased mortality risk in older gravidas –Increased risk in pregnancy with new partner multiparas have increased risk with preexisting hypertension, renal disease, diabetes mellitus preeclampsia is a leading case of direct maternal mortality

18. Preeclampsia Morbidity & Mortality Maternal – Stroke (sBP > 160 mm Hg) – Pulmonary edema – Jaundice – Seizure (eclampsia) – Placental abruption – Acute renal failure Fetal – Oligohydramnios – Intrauterine growth restriction (SGA) – Metabolic acidosis 5 minute APGARS <3 Requiring respiratory ventilation at birth – Fetal death

19. Assessment of woman - Clinical Blood Pressure –assess severity –ensure consistency in measuring –relationship of high BP to DIC not seizure Cardiorespiratory –chest pain –dyspnea –distended neck veins

20. Assessment of woman – Clinical (cont’d) Central Nervous System –presence and severity of headache –vision disturbances – blurring, scotomata –tremulousness, irritability, somnolence –hyperreflexia Hematologic –bleeding, petechiae Hepatic –RUQ and epigastric pain –nausea and vomiting Renal –urine output and colour

21. Assessment of woman - Laboratory Hematologic – hemoglobin, platelets (HELLP), blood film – PTT, INR, fibrinogen, FDP – LDH (HELLP), uric acid, bilirubin Hepatic –ALT, AST (HELLP) –glucose and ammonia to rule out AFLP Renal – proteinuria – creatinine, urea, uric acid

22. Assessment of Fetus Fetal movement Fetal heart rate assessment, by auscultation or EFM Fetal growth assessment by fundal height measurement or ultrasound Where resources exist: – Biophysical profile (BPP) – Amniotic fluid volume (AFV)

23. Maternal Stress Reduction Component of maternal BP is adrenergic Maternal discomfort must be minimized Several components –well planned management protocol (team approach) –clear explanation of plan to woman/family –quiet, dimly lit, isolated room –minimization of negative stimuli

24. Management of symptoms Nausea and vomiting – antiemetic of choice Maternal pain (headache, RUQ or epigastric pain) – morphine 2 – 4 mg IV – antacid – minimize palpation

25. Anti-hypertensive therapy - Goals minimize risk of maternal cerebro-vascular accident prevent placental abruption gain time for further assessment and treatment –stabilize for transfer to higher level facility, if needed –facilitate vaginal delivery when possible –prolong gestation where appropriate/feasible

26. Anti-hypertensive agents Labetalol (Trandate®, Normodyne®) Hydralazine (Apresoline®) Nifedipine (Adalat-PA®) Clonidine

27. Anti-hypertensive agents Hydralzine direct arteriolar vasodilator rapid onset of action useful for hypertensive crisis can be used orally or via IV should not be first choice due to high rate of maternal/fetal adverse effects

28. Anti-hypertensive agents Hydralzine (cont’d) Dosage: –5 mg IV test dose, followed by 5 – 10 mg IV q 20 min. –infusion 0.5 – 10 mg/hour Caution: unpredictable hypotension with resulting fetal compromise Side Effects: flushing, headache, and maternal tachycardia

29. Anti-hypertensive agents Labetalol Combined α and β-blocker with Intrinsic Sympathetic Activity Rapid onset of action useful for hypertensive crisis Can be used orally or via IV

30. Anti-hypertensive agents Labetalol Dosage: maximum 300 mg IV dose –bolus 10 – 20 mg IV q 10 min. up to 300 mg –infusion 1 – 2 mg/min., increasing by 1 mg/ q 15 min. to a maximum of 4 mg/min. IB titrated to BP Caution: asthma Side Effects: fetal bradycardia Benefits: dependable, familiar

31. Anti-hypertensive agents Nifedipine Calcium channel blocker Direct relaxation of vascular smooth muscle Oral agent Not sub-lingual administration

32. Anti-hypertensive agents Nifedipine Dosage: –Adalat PA 10 mg bid may increase to 40 mg bid –Adalat XL starting dose 30 mg/day Caution: magnesium toxicity (?) with use of Adalat and MgSO4 in combination Side Effects: flushing, headache, palpitations, tocolysis

33. Anti-hypertensive agents Clonidine Potent α-2-adrenoceptor central stimulant Used to treat mild and moderate hypertension Dosage: –150 µg infused in normal saline –Per os: 0.1 mg to 0.2 mg twice a day Side Effects: sedation, dry mouth

34. Seizures Blood pressure not a reliable predictor of who will have seizures No benefit to prophylaxis in absence of proteinuria High ‘number needed to treat’ to prevent seizure agents not innocuous nor completely effective MgSO₄ is agent of choice when seizure prophylaxis is felt to be indicated

35. Seizures – Possible complications Fetal bradycardia (more than 50%) Placenta abruptio (10% to 20%) Aspiration pneumonia (5% to 10%) Cerebral hemorrhage, especially in the older woman Temporary loss of sigh with progressive recovery within one week (10%) Coma due to the cerebral edema (5%) Psychosis that can last 2 weeks (less than 5%)

36. Seizures - Management Magnesium sulfate (MgSO₄) – agent of choice for prophylaxis and termination of seizures – will control seizures within 1 to 2 hours – most woman will regain consciousness and orientation – Superior to phenytoin for prophylaxis – superior to phenytoin or diazepam in preventing recurrence – decreased maternal morbidity and mortality with use for cessation of seizure activity – no difference in perinatal mortality – should be on ‘essential drug list’ in every country

37. Seizures - Management Magnesium sulfate Loading Dose: –4 g IV (20 ml of 20% solution) slowly over 20 min. –followed by 1 – 4 g / hour IV OR –5 g IM (10 ml of 50% solution) with 1 ml of 20% lidocaine in same syringe twice, each side –followed by 5 g IM q 4 h

38. Seizures - Management Magnesium sulfate Side Effects: weakness, paralysis, cardiac toxicity Monitor: reflexes, respiration, level of consciousness CAUTION: Confirm the concentration of this medication when calculating the dosage

39. Seizures - Management Magnesium sulfate Overdose: observe closely for possible side effects including weakness, respiratory paralysis, somnolence especially high risk in those with oliguria or those receiving calcium channel blockers ANTIDOTE stop magnesium sulfate infusion give calcium gluconate 1g IV (10 ml of 10% solution) over 10 minutes

40. Seizures – Management protocols Every labour and delivery unit should establish and post protocols for the use of magnesium sulfate. Parameters should include: Preparation of medication Assessments required prior to administration Administration protocol Assessment for side effects Management of toxicity Documentation

41. Seizures – Differential diagnosis When magnesium sulfate therapy fails to control seizures, consider other possible causes: chronic epilepsy encephalitis meningitis cerebral tumor cerebral vascular malformation (aneurysm) secondary cerebral abscesses due to parasitic or fungal infections severe malaria

42. Transport Consider transport only if local resources limited and maternal/fetal condition permits Stable maternal BP Reassuring fetal status Administer appropriate anti-hypertensive agents Give MgSO₄, if appropriate Consult with referral centre and woman/family Woman should be transported on her left side, accompanied by skilled birth attendant

43. Delivery – “The Cure” Timely delivery minimizes maternal and neonatal morbidity and mortality Optimize maternal status before interventions to deliver Delay delivery to gain fetal maturity and to allow transfer only when maternal and fetal condition permit Gestational hypertension is a progressive disease, expectant management is potentially harmful in presence of severe disease or suspected fetal compromise

44. When to deliver ≥37 weeks with gestational hypertension ≥34 weeks with severe gestational hypertension <34 weeks with any of: –poorly controlled diastolic BP –laboratory evidence of worsening end-organ involvement –suspected fetal compromise –uncontrolled seizures –symptoms unresponsive to appropriate therapy

45. Management - Overview stress reduction (helps in 50% of cases) clinical and laboratory assessment of mother and fetus treat blood pressure if diastolic BP ≥ 110 mmHg treat nausea and vomiting, and other symptoms including pain effectively consider seizure prophylaxis consider timing and mode of delivery (induction) consider transfer to referral center, if applicable closely monitor the woman in the early post-partum

46. Case: A 32 year old G2P1 woman presents for her routine prenatal visit at 32 weeks’ gestation. Her blood pressure is 140/90. In the past, throughout her pregnancy it has been 115/75 to 130/85. Her weight is 105 kg. What steps do you perform as part of your initial investigation?

47. Case: Repeat measurement in ≥ 4 hour intervals unless very high Assess for proteinuria (urine dip stick) Question woman about any signs and symptoms of gestational diabetes Order initial blood work: (liver function test, uric acid, platelets)

48. Case (cont’d) Repeat blood pressures over the next three hours range from 140/90 to 155/95 Urine dip stick: 3+ What is your management plan?

49. Case: Delivery is the cure Monitor blood pressure and control with medications if necessary Monitor fetal well being

50. Key Messages Health care providers must be able to promptly recognize the various presentations of hypertension in pregnancy. Health care providers must be able to identify appropriate monitoring and management of gestational hypertension, including having a plan for referral and transfer to a higher-level health care facility when needed.

51. Key Messages (cont’d) Health care providers must be able to take emergency measures to stop seizure activity, and to stabilize the woman. Magnesium sulfate is a cost effective and life- saving drug. Health care providers must advocate with national health authorities to ensure a continuous and an uninterrupted supply of this medication as part of their safe motherhood programs.