1. Headache, Blurred Vision, Convulsions, Loss of Consciousness or Elevated Blood Pressure Advances in Maternal and Neonatal Health

2. 2Headaches, Elevated Blood Pressure and Convulsions Session Objectives Discuss best practices for diagnosing and managing hypertension, pre-eclampsia and eclampsia Describe strategies for controlling hypertension Describe strategies for preventing and treating convulsions in pre-eclampsia and eclampsia

3. 3Headaches, Elevated Blood Pressure and Convulsions Problem Pregnant or recently postpartum woman who: Has elevated blood pressure Complains of headache or blurred vision Is found unconscious or convulsing

4. 4Headaches, Elevated Blood Pressure and Convulsions Elevated Blood Pressure Classifications: Chronic hypertension Pregnancy-induced hypertension –Pregnancy-induced hypertension without proteinuria –Mild pre-eclampsia –Severe pre-eclampsia –Eclampsia

5. 5Headaches, Elevated Blood Pressure and Convulsions Pre-Eclampsia Woman over 20 weeks gestation with: Diastolic blood pressure > 90 mm Hg AND Proteinuria Predisposes woman to develop eclampsia

6. 6Headaches, Elevated Blood Pressure and Convulsions Mild Pre-eclampsia Two readings of diastolic blood pressure 90-110 mm Hg 4 hours apart after 20 weeks gestation Proteinuria up to 2+ No other signs/symptoms of severe pre-eclampsia

7. 7Headaches, Elevated Blood Pressure and Convulsions Severe Pre-eclampsia Diastolic blood pressure > 110 mm Hg Proteinuria > 3+ Other signs and symptoms sometimes present: Epigastric tenderness Headache Visual changes Hyperreflexia Pulmonary edema Oliguria

8. 8Headaches, Elevated Blood Pressure and Convulsions Predicting Pre-eclampsia Using Risk Factors: Study Objective and Design Objective: To determine if risk factors for pre-eclampsia could be used to predict who develops it Design: Combined retrospective and prospective analysis Saudan et al 1998.

9. 9Headaches, Elevated Blood Pressure and Convulsions Predicting Pre-eclampsia Using Risk Factors: Study Definitions Gestational hypertension was defined as the onset of hypertension (systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg) after 20 weeks gestation Pre-eclampsia was diagnosed by standard criteria Saudan et al 1998.

10. 10Headaches, Elevated Blood Pressure and Convulsions Predicting Pre-eclampsia Using Risk Factors: Results No significant difference in age, parity, gestational age, diastolic blood pressure at presentation or history of diabetes. PredictorCombined dataSignificance Gestation at presentation 0.82 (0.77-0.87)p < 0.0001 Saudan et al 1998.

11. 11Headaches, Elevated Blood Pressure and Convulsions Predicting Pre-eclampsia Using Risk Factors: Conclusion Those women who developed gestational hypertension at an earlier gestational age were more likely to progress to pre- eclampsia.

12. 12Headaches, Elevated Blood Pressure and Convulsions Gestational Hypertension and Predicting Pre-eclampsia: Objective and Design Objective: To determine if there is a “cut off” level of blood pressure which can be used to predict pre-eclampsia Design: Cohort study; Blood pressure was recorded in 1000 consecutive pregnancies at each antenatal visit until delivery and at the postpartum visit Moutquin et al 1985.

13. 13Headaches, Elevated Blood Pressure and Convulsions Gestational Hypertension and Predicting Pre-eclampsia: Results Weeks Gestation (9–28) Average Sensitivity Positive Predictive Value 130 mm Hg Systolic BP46.114.3 80 mm Hg Diastolic BP41.421.7 Moutquin et al 1985.

14. 14Headaches, Elevated Blood Pressure and Convulsions Gestational Hypertension and Predicting Pre-eclampsia: Conclusions Approximately 15 – 25% of women initially diagnosed with gestational hypertension will develop pre-eclampsia It is difficult to predict who will develop pre-eclampsia Moutquin et al 1985; Saudan 1998.

15. 15Headaches, Elevated Blood Pressure and Convulsions Eclampsia Convulsions occurring after 20 weeks gestation in a woman without a previously known seizure disorder A small proportion of women with eclampsia have normal blood pressure

16. 16Headaches, Elevated Blood Pressure and Convulsions Strategies for Preventing Eclampsia Antenatal care and recognition of hypertension Identification and treatment of pre-eclampsia by skilled attendant Timely delivery 3.4% of women with severe pre-eclampsia will have a convulsion Eclampsia is the number one cause of in-hospital maternal death in Nepal

17. 17Headaches, Elevated Blood Pressure and Convulsions Predicting Eclampsia Study: Objective and Design Objective: Investigate potential usefulness of average mean arterial pressure, maximum mean arterial pressure and maximum diastolic pressure in the second trimester to predict the development of pre-eclampsia Design: Retrospective analysis Chesley and Sibai 1987.

18. 18Headaches, Elevated Blood Pressure and Convulsions Predicting Eclampsia Study: Results 207 nulliparas and 20 multiparas developed eclampsia Average mean arterial pressure in 2 nd trimester  90 mm Hg: 22% of nulliparas 30% of multiparas Maximum mean arterial pressure in 2 nd trimester  90 mm Hg: 34% nulliparas 35% multiparas Maximum diastolic pressure  80 mm Hg: 8.2% nulliparas 30% multiparas Maximum diastolic pressure  90 mm Hg: 0% nulliparas 5% multiparas Chesley and Sibai 1987.

19. 19Headaches, Elevated Blood Pressure and Convulsions Predicting Eclampsia Study: Conclusions Cannot use 2 nd trimester mean arterial pressure or diastolic pressure to predict eclampsia Eclampsia is abrupt in onset, without warning signs in about 20% of women

20. 20Headaches, Elevated Blood Pressure and Convulsions Initial Assessment and Management of Eclampsia Shout for help - mobilize personnel Rapidly evaluate breathing and state of consciousness Check airway, blood pressure and pulse Position on left side Protect from injury but do not restrain Start IV infusion with large bore needle (16-gauge) Give oxygen at 4 L/minute DO NOT LEAVE THE WOMAN UNATTENDED

21. 21Headaches, Elevated Blood Pressure and Convulsions Antihypertensive Drugs Hydralazine Labetolol Nifedipine Principles: Initiate antihypertensives if diastolic blood pressure > 110 mm Hg Maintain diastolic blood pressure 90-100 mm Hg to prevent cerebral hemorrhage

22. 22Headaches, Elevated Blood Pressure and Convulsions Management During a Convulsion Give magnesium sulfate IM Gather emergency equipment (O2, mask, etc) Position on left side Protect from injury but do not restrain DO NOT LEAVE THE WOMAN UNATTENDED

23. 23Headaches, Elevated Blood Pressure and Convulsions Anticonvulsive Drugs Magnesium sulfate Diazepam Phenytoin

24. 24Headaches, Elevated Blood Pressure and Convulsions Post-convulsion Management Prevent further convulsions Control blood pressure Prepare for delivery (if undelivered)

25. 25Headaches, Elevated Blood Pressure and Convulsions Studies to be Reviewed For severe pre-eclampsia Magnesium sulfate vs. placebo For eclampsia Magnesium sulfate vs. diazepam Magnesium sulfate vs. phenytoin Magnesium sulfate and outcome of labor

26. 26Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate Use magnesium sulfate in Women with eclampsia Women with severe pre-eclampsia necessitating delivery Start magnesium sulfate when decision for delivery is made Continue therapy until 24 hours after delivery or the last convulsion, whichever occurs last

27. 27Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Placebo in Women With Pre-Eclampsia: Objective and Design Objective: To evaluate the effectiveness of magnesium sulfate vs. placebo Design: Double-blinded prospective randomized controlled trial Tertiary referral obstetrics unit in South Africa 822 women with severe pre-eclampsia necessitating delivery randomly assigned to placebo or magnesium sulfate Data from 699 women evaluated Coetzee, Domisse and Anthony 1998.

28. 28Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Placebo in Women With Pre-Eclampsia: Results In women with severe pre-eclampsia, eclampsia occurred 11 times less often in women receiving magnesium sulfate than in women receiving placebo Coetzee, Domisse and Anthony 1998.

29. 29Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Placebo in Women With Pre-Eclampsia: Results (continued) ConvulsionsNo Convulsions Magnesium sulfate1 (0.3%)344 (99.7) No magnesium sulfate11 (3.2%)*329 (96.7%) Coetzee, Domisse and Anthony 1998. * RR 0.09, 95% CI (0.01–0.69)

30. 30Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Placebo in Women With Pre-Eclampsia: Results (continued) No significant difference in: Need for antihypertensive therapy Number of cesarean sections performed Number of Live births vs. stillbirths Average gestational age Birthweight at delivery Number of maternal deaths Coetzee et al 1998.

31. 31Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Diazepam for Eclampsia: Study Objective and Design Objective: To assess effects of magnesium sulfate compared with diazepam when used for the care of women with eclampsia Design: Randomized controlled trial Duley and Henderson-Smart 2000a.

32. 32Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Diazepam: Recurrence of Convulsions ConvulsionsNo convulsionsTotal Magnesium sulfate 71547618 Diazepam160458618 RR 0.45, 95% CI 0.35-0.58 No differences in maternal morbidity and borderline decrease in maternal mortality Duley and Henderson-Smart 2000a.

33. 33Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Phenytoin for Eclampsia: Study Objective and Design Objective: To assess the effects of magnesium sulfate compared with phenytoin when used for the care of women with eclampsia Design: Randomized controlled trial Duley and Henderson-Smart 2000b.

34. 34Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Phenytoin: Results 4 trials, 823 women Magnesium sulfate was associated with a reduction in the recurrence of convulsion when compared to phenytoin (RR 0.30, 95% CI 0.20–0.46) Magnesium sulfate was also associated with reduced risks of pneumonia (RR 0.66, 95% CI 0.49–0.90) and intensive care unit stay (RR 0.67, 95% CI 0.50–0.89) Magnesium sulfate reduced the need for babies’ admission to intensive care unit, reduced duration of stay or death in intensive care unit Duley and Henderson-Smart 2000b.

35. 35Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Phenytoin: Recurrence of Convulsions ConvulsionsNo convulsionsTotal Magnesium sulfate 23400423 Phenytoin73349422 RR 0.30 95% CI 0.20–0.46 Duley and Henderson-Smart 2000b.

36. 36Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Phenytoin: Pneumonia PneumoniaNo pneumoniaTotal Magnesium sulfate 15373388 Phenytoin34353387 RR 0.44 95% CI 0.24–0.79 Duley and Henderson-Smart 2000b.

37. 37Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Phenytoin: Admission to Neonatal Intensive Care Unit NICUNo NICUTotal Magnesium sulfate 65323388 Phenytoin97290387 RR 0.67 95% CI 0.50–0.89 Duley and Henderson-Smart 2000b.

38. 38Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate vs. Phenytoin for Eclampsia: Conclusion Magnesium sulfate appears to be substantially more effective and safer than phenytoin for treatment of eclampsia Duley and Henderson-Smart 2000b.

39. 39Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate and Outcome of Labor: Objective and Design Objective: To evaluate the outcome of labor in women receiving magnesium sulfate vs. phenytoin. Design: 2138 women were randomly assigned to magnesium sulfate or phenytoin for prevention of eclampsia 905 nulliparous women met the inclusion criteria: 480 women received phenytoin 425 women received magnesium sulfate Leveno et al 1998.

40. 40Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate and Outcome of Labor: Results Labor CharacteristicMagnesium sulfate (n=425) Phenytoin (n=480) Significance Therapeutic oxytocin325 (76%)350 (73%)Not significant Admission to delivery (hours, mean  SD) 12.8  713.1  7 Not significant Prolonged second stage35 (8)33 (7)Not significant Cesarean delivery (total)78 (18)85 (18)Not significant Cesarean delivery (dystocia)62 (15)66 (14)Not significant Leveno et al 1998.

41. 41Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate and Outcome of Labor: Conclusion There is no clinical evidence that magnesium sulfate given for intrapartum management of pregnancy-induced hypertension had any effect on the outcome of labor Leveno et al 1998.

42. 42Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate and Effect on Labor: Objective and Design Objective: Evaluate effect of magnesium sulfate on labor Design: Study period: March 1995 to June 1996; randomized term mildly pre-eclamptic women to receive magnesium sulfate 6 g bolus then 2 g/hour or saline Cervical ripening agents/oxytocin at physician’s discretion Women taken off protocol if developed severe pre- eclampsia Witlin, Friedman and Sibai 1997.

43. 43Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate and Effect on Labor: Results Outcome: Length of labor, duration of latent and active phases, first and second stages Results: No difference in duration of oxytocin: magnesium sulfate group 14.1 hours vs. 13.5 hours Slightly higher dose of oxytocin required in magnesium sulfate group: 13.9 mU/min vs. 11.0 (p=0.036) No significant postpartum hemorrhage or side effects Witlin, Friedman and Sibai 1997.

44. 44Headaches, Elevated Blood Pressure and Convulsions Magnesium Sulfate and Effect on Labor: Conclusion Slightly higher doses of oxytocin required in magnesium treated groups, but no difference in labor and no adverse effects Witlin, Friedman and Sibai 1997.

45. 45Headaches, Elevated Blood Pressure and Convulsions Monitoring Hourly AssessNormal Findings Level of consciousnessSleepy but arousable Diastolic blood pressure Should be maintained between 80–100 mm Hg Respiratory rate16 breaths/minute or more Deep tendon reflexesMinimal but present Fetal heart sounds (if undelivered)Decrease in variability

46. 46Headaches, Elevated Blood Pressure and Convulsions Monitoring Hourly AssessAbnormal FindingsManagement LungsPulmonary edema Discontinue magnesium sulfate Urine output Falls below 30 mL/hour or 120 mL/4 hours Discontinue magnesium sulfate Uterus (after delivery) Atonic uterus (postpartum bleeding) Consider oxytocin for 24 hours after delivery

47. 47Headaches, Elevated Blood Pressure and Convulsions Principles of Management Timing and route of delivery: condition of mother vs. maturity of fetus Assessment of fetus: evidence of fetal compromise Control of convulsions Control of hypertension Referral due to other organ complications: pulmonary, renal, central nervous system

48. 48Headaches, Elevated Blood Pressure and Convulsions Summary There are many manifestations of increased blood pressure in pregnancy It is not possible to predict which patients are at risk for severe pre-eclampsia or eclampsia Vigilant care is needed to make the diagnosis Once the diagnosis is made, appropriate treatment can reduce morbidity and mortality Anticonvulsants should be used, with magnesium sulfate being the first line Antihypertensives should be employed as needed Close monitoring is needed for side effects

49. 49Headaches, Elevated Blood Pressure and Convulsions References American College of Obstetricians an Gynecologists. 1996. Technical Bulletin Hypertension in Pregnancy. #219. Chesley LC and BM Sibai. 1987. Blood pressure in mid-trimester and future eclampsia. Am J Obstet Gynecol 157(5): 1258–1561. Coetzee E, J Dommisse and J Anthony. 1998. A randomised controlled trial of intravenous magnesium sulphate versus placebo in the management of women with severe pre-eclampsia. Br J Obstet Gynaecol 105: 300–303. Duley L and D Henderson-Smart. 2000a. Magnesium sulphate versus diazepam for eclampsia (Cochrane Review), in The Cochrane Library, Issue 4. Update Software: Oxford. Duley L and D Henderson-Smart. 2000b. Magnesium sulphate versus phenytoin for eclampsia (Cochrane Review), in The Cochrane Library, Issue 4. Update Software: Oxford.

50. 50Headaches, Elevated Blood Pressure and Convulsions References (continued) Leveno KJ et al. 1998. Does magnesium sulfate given for prevention of eclampsia affect the outcome of labor? Am J Obstet Gynecol 178(4): 707 – 712. Moutquin J et al. 1985. A prospective study of blood pressure in pregnancy: Prediction of preeclampsia. Am J Obstet Gynecol 151: 191 – 196. Saudan P et al. 1998. Does gestational hypertension become pre- eclampsia? Br J Obstet Gynaecol 105: 1177-1184. Szal SE, MS Croughan-Minihane and SJ Kilpatrick. 1999. Effect of magnesium prophylaxis and preeclampsia on the duration of labor. Am J Obstet Gynecol 180: 1475 – 1479. Villar MA and BM Sibai. 1989. Clinical significance of elevated mean arterial blood pressure in second trimester and threshold increase in systolic and diastolic blood pressure during third trimester. Am J Obstet Gynecol 160: 419 – 423. Witlin AG, SA Friedman and BM Sibai. 1997. The effect of magnesium sulfate on the duration of labor in women with mild preeclampsia at term: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol 176(3): 623 – 627.