Hypertensive Disorders in Pregnancy

1. Hypertensive Disorders in Pregnancy John Bettler October 4, 2018

2. Pre-test

3. Objectives • Review definitions/diagnostic criteria of hypertensive disorders in pregnancy • Review recommendations for preeclampsia prevention strategies • Review antenatal surveillance • Review treatment (antepartum/intrapartum/postpartum)

4. Case 1

5. Definitions • Chronic Hypertension • Gestational Hypertension • Preeclampsia • Chronic hypertension with superimposed preeclampsia • Eclampsia • HELLP Syndrome

6. Definitions • Chronic Hypertension -2 or more BP >140 SBP or 90 DBP taken at least 4 hours apart diagnosed prior to pregnancy, before 20 weeks gestation or persists greater than 12 weeks postpartum. • Gestational Hypertension • Preeclampsia • Chronic hypertension with superimposed preeclampsia • Eclampsia • HELLP Syndrome

7. Definitions • Chronic Hypertension • Gestational Hypertension - Elevated BP diagnosed after 20 weeks without proteinuria. • Preeclampsia • Chronic hypertension with superimposed preeclampsia • Eclampsia • HELLP Syndrome

8. Definitions • Chronic Hypertension • Gestational Hypertension • Preeclampsia - Elevated BP with proteinuria or without proteinuria if other lab abnormalities present • Chronic hypertension with superimposed • Eclampsia • HELLP Syndrome

9. Definitions • Chronic Hypertension • Gestational Hypertension • Preeclampsia • Chronic hypertension with superimposed preeclampsia - Rise of SBP >30 mm, DBP >15 or development of proteinuria or symptoms/lab tests c/w preeclampsia with severe features or HELLP. • Eclampsia • HELLP Syndrome

10. Definitions • Chronic Hypertension • Gestational Hypertension • Preeclampsia • Chronic hypertension with superimposed preeclampsia • Eclampsia - convulsions or coma unrelated to known CNS disorder and with signs and symptoms of preeclampsia. • HELLP Syndrome

11. Definitions • Chronic Hypertension • Gestational Hypertension • Preeclampsia • Chronic hypertension with superimposed preeclampsia • Eclampsia • HELLP Syndrome - (better called multisystem disease) Hemolysis, Elevated Liver enzymes, Low Platelets.

12. Chronic hypertension treatment • Threshold for treatment initiation = 150/100 • Antihypertensives • Methyldopa, labetalol, and nifedipine • Thiazides may be continued • Contraindicated: ACE-I/ARB, Atenolol • Surveillance • Urinalysis at each visit for proteinuria (?) • Growth ultrasounds starting @ 24 weeks (+dopplers if concern for IUGR) • Antenatal testing if on meds or any complications • NST twice weekly starting @ 32 weeks • AFI weekly starting @ 32 weeks • IOL @ 38-39 wks

13. potential COMPLICATIONS OF CHRONIC HTN • Superimposed preeclampsia (13-40%) • Cesarean section (OR 2.7) • Postpartum hemorrhage (OR 2.2) • GDM (OR1.8) • Abruptio placentae (OR ~3) • Perinatal death • Fetal growth restriction

14. Prevention of Preeclampsia - Cochrane

16. ACOG COMMITTEE OPINION, July 2018 One or more More than one Low-dose aspirin use during pregnancy. ACOG Committee Opinion No. 743. American College of Obstetricians and Gynecologists. ObstetGynecol 2018;132:e44–52.

17. Case 2

18. Diagnostic Criteria for Pre-eclampsia • Blood pressure • ≥ 140 SBP or ≥ 90 DBP on two occasions at least 4 hours apart after 20 weeks GA in woman w/o h/o HTN • ≥160 SBP or ≥ 110 DBP “confirmed within a short interval (minutes)” AND • Proteinuria: • ≥300 mg /24 hr urine collection or • Protein/creatinine ≥0.3 mg/dL • Dipstick reading of 1+ (“used only if other quantitative methods not available”) OR • Absence of proteinuria but new onset of any of the severe features

19. Preeclampsia work-up • Labs • Urine P/C or 24hr urine prot. • Order the P/C ratio separately as STAT “protein, random urine” and STAT “creatinine, random urine” because the results return quickly • CBC (plts) • Serum Cr • AST, ALT • Uric acid (indicator of renal function) • LDH (indicator of microangiopathic hemolysis)

20. Management of Preeclampsia w/o sf • Expectant management before 37 weeks • Closely watch for development of severe features • Twice weekly BP measurements • Antepartum surveillance • Non-stress tests (NST’s), amniotic fluid measurement, biophysical profile • Growth ultrasound every 3 to 4 weeks with dopplers • Weekly labs (No need to follow urine) • Delivery at 37 weeks

21. Case 3

22. Severe features • SBP ≥ 160 or DPB ≥ 110 • Progressive renal insufficiency with Cr >1.1 mg/dl or doubled from baseline assuming no other renal disease • Cerebral or visual disturbance • Impaired liver function • Low platelets <100,000 • Pulmonary edema Proteinuria is not necessary for the diagnosis of preeclampsia if there is new-onset HTN with one of the severe features listed above.

23. Characterization of Symptoms Immediately Preceding Eclampsia • 3,267 deliveries and 46 cases of eclampsia (1.4%) • Most common prodromal neurological symptoms (regardless of the degree of hypertension OR whether the seizure occurred antepartum or postpartum): • Headaches (80%) • Visual disturbance (45%), • 20% of women with eclampsia reported no neurologic symptoms before the seizure Cooray SD, Edmonds SM, Tong S, et al. Characterization of Symptoms Immediately Preceding Eclampsia. Obstetrics & Gynecology, Vol 118(5):1000-1004, November 2011. 43

24. Intrapartum treatment for severe features • Antihypertensives • Seizure prophylaxis • Monitoring/Documentation • Contact MCH Fellow for consult (minimum of Category C)

26. OB Pre-eclampsia or Hypertension

27. Intrapartum treatment for severe features • Antihypertensives • Seizure prophylaxis • Monitoring/Documentation

29. antihypertensive Key Clinical Pearl • The critical initial step in decreasing maternal morbidity and mortality is to administer anti-hypertensivemedications within 60 minutes of documentation of persistent (retested within 15 minutes) BP ≥160 systolic, and/or >105-110 diastolic. • Ideally, antihypertensive medications should be administered as soon as possible, and availability of a “preeclampsia box” will facilitate rapid treatment. • In Martin et al., stroke occurred in: • 23/24 (95.8%) women with systolic BP > 160mm Hg • 24/24 (100%) had a BP ≥ 155 mm Hg • 3/24 (12.5%) women with diastolic BP > 110mm Hg • 5/28 (20.8%) women with diastolic BP > 105mm Hg Martin JN, Thigpen BD, Moore RC, Rose CH, Cushman J, May. Stroke and Severe Preeclampsia and Eclampsia: A Paradigm Shift Focusing on Systolic Blood Pressure, ObstetGynecol 2005;105-246. 48

30. Hypertensive Medication Administration Oral v. IV • IV Hydralazine • Onset: 5-20 min • Peak: 15-30 min • PO Nifedipine • Onset: 5-20 min* • Peak: 30-60 min • IV Labetalol • Onset: 2-5 min • Peak: 5 min • PO Labetalol: • Onset: 20 min-2 hrs • Peak: 1-4 hrs *PO, (oral) not sublingual nifedipine, onset of action is 15-30 minutes depending on the reference source. * Cohan J, Checcio L. Nifedipine in the Management of Hypertensive Emergencies: Report of Two Cases and Review of the Literature. 1985 Nov;3(6):524-30 Raheem I, Saiid R, Omar S, et al. Oral nifedipine versus intravenous labetalol for acute blood pressure control in hypertensive emergencies of pregnancy: a randomized trial. BJOG 2012;119:78-85. http://www.uspharmacist.com/content/d/feature/i/1444/c/27112/ Current Cardiovascular Drugs, edited by William H. Frishman, Angela Cheng-Lai, James Nawarskas, 4th edition 2005 pg. 2-186 51

31. Intrapartum treatment for severe features • Antihypertensives • Seizure prophylaxis • Monitoring/Documentation

32. Magnesium sulfate • Treatment of choice in women who have preeclampsia with severe features • prevent eclamptic seizures (NNT = 100) • placental abruption (NNT = 100) • Loading dose • 4-6 gm IV over 10 minutes • Continuous drip • 2gm/hr

33. Magnesium Sulfate in the Management of Preeclampsia Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulfate? • 58% reduction in seizures • 45% reduction in maternal death* • 33% reduction in placental abruption *The 45% reduction in maternal death is not statistically significant but clinically important. Altman D, Carroli G, Duley L, et al. The Magpie Trial: a randomized placebo-controlled trial; Lancet 2002;359:1877–90. 55

34. Intrapartum treatment for severe features • Antihypertensives • Seizure prophylaxis • Monitoring/Documentation

35. Magnesium monitoring/documentation • PIH labs q 6 hours • Monitoring for worsening dz and mag toxicity: • Limit input (<100 cc/hr IV and <125 125 cc/hr IV+PO) • urine output (≥ 30 cc/hr or 100 cc over 4 hrs) • DTR’s • Respiratory status (RR >12 and auscultation for pulmonary edema) • Mental status • FHTs (moderate variability) • Mag levels are usually only checked if there are concerns or known elevated Cr • Intrapartum notes • Q 2 hours

36. Magnesium serum Levels Antidote = calcium gluconate 1 gm IV over 3 min

37. Case 4

39. OB Postpartum Pre-eclampsia or Hypertension

40. Postpartum Care • Blood pressure goals • Antihypertensives • Seizure prophylaxis • Period of observation

41. Postpartum Care • Blood pressure goals • Antihypertensives • Seizure prophylaxis • Period of observation

42. Postpartum Blood pressure goals • SBP > 150/100 on serial measurements (interval of measurements and whether to start immediately or follow a few BPs depends on how high it is initially)

43. Postpartum Care • Blood pressure goals • Antihypertensives • Seizure prophylaxis • Period of observation

44. Postpartum antihypertensives • If you think BP meds need to be started PP, discuss w/ MCH fellow re. which med to use • Initial options for treatment; • Oral nifedipine 10mg immediate release given serially to determine total needed dose • Oral nifedipine XL 30 mg daily • Oral labetalol 100-200 mg TID • If HTN persists > 24 hours avoid NSAIDS

45. Postpartum Care • Blood pressure goals • Antihypertensives • Seizure prophylaxis • Period of observation

46. Postpartum seizure prophylaxis • Magnesium for 12-24 hours after delivery, depending on clinical course • At UNM duration of magnesium infusion is usually 24 hours • Diuresis (greater than 4 L/day) is believed to be the most accurate clinical indicator of resolution of preeclampsia/eclampsia, but is not a guarantee against the development of seizures

47. Postpartum Care • Blood pressure goals • Antihypertensives • Seizure prophylaxis • Period of observation

48. Postpartum observation • Inpatient • 72 hours after delivery for gestational HTN or preeclampsia • Do not discharge patient until BP is well controlled for at least 24 hours • Outpatient • 7–10 days after delivery • Earlier in women with symptoms or whose BPs were difficult to control or labile in the postpartum period • If elevated BPs persist at 6-8 weeks postpartum, the diagnosis is chronic HTN (which we already knew she had, so the need for ongoing med tx is not unexpected)

49. Long-term implications • 2X increased risk of later-life CV disease (MI, CVA, CHF) in all pre-e based on large epidemiological studies • Increased risk of preeclampsia in future pregnancies • Make sure she is on reliable contraception to space pregnancies • Optimize risk factors prior to next pregnancy • Seek medical care as soon as she knows she is pregnant • Patients should be advised: • Maintain ideal body weight • Aerobic exercise 5X/wk • Diet high in fiber/vegetables/fruits, low in fat • Avoid tobacco

50. Post-test