hypertension crisis and management with hypertensive medicication

Hypertensive crises

1. Marwan Alhalabi MD PhD Professor in Reproductive Medicine Faculty of Medicine Damascus University And Medical Director Orient Hospital Assisted Reproduction Center Damascus – Syria

2. Hypertensive disorders are the most common and yet serious conditions seen in obstetrics

3. Incidence is 5- 10%. The most frequent cause of iatrogenic prematurity . Preterm delivery Intrauterine growth restriction (IUGR) Perinatal death Maternal cerebrovascular accidents ( CVA) . Placental abruption.

4. Decreases during the first trimester, Reaching its lowest point at 20 weeks , Returns to pre- pregnancy levels during the third trimester .

5. Classification Pre- eclampsia Eclampsia Preeclampsia superimposed on chronic hypertension Chronic hypertension with pregnancy Gestational hypertension

6. Blood Pressure ≥ 140/90mmHg on two or more occasions in a previously normotensive patient after 20 weeks gestation without proteinuria returning to normal 12 weeks after delivery Almost half of these develop preeclampsia syndrome

7. GESTATIONAL HYPERTENSION GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION ( ≥ 140/90 ) No proteinuria

8. DEFINITION SYMPTOMS EXAMINATION Sustained B.P No proteinuria NONE Unremarkable GESTATIONAL HYPERTENSION GESTATIONAL HYPERTENSION

9. CRITERIA FOR MILD GESTATIONAL HYPERTENSION Blood Pressure > 140 to < 160 mm Hg, systolic > 90 to < 110 mm Hg, diastolic Proteinuria < 300 mg per 24-hr collection Platelet count > 100,000/mm3 Liver enzymes Normal Maternal symptoms Absent IUGR / Oligohydramnios Absent

10. It is defined as hypertension of at least 140/90mm Hg recorded on two separate occasions at least 4 hours apart and in the presence of at least 300mg protein in a 24 hour collection of urine, arising after the 20 th week of gestation in a previously normotensive woman and resolving completely by the 6 th postpartum week .

11. Preeclamsia Gestational Hypertension Proteinuria

12. DEMOGRAPHIC OBSTETRICS MEDICAL NULLIPARA (Age extremes <20yrs , >35yrs ) Multiple gestation Molar pregnancy Non- immune hydrops Diabetes mellitus Chronic HTN Renal disease SLE RISK FACTORS for PREECLAMPSIA

13. Genetic Genetic Predisposition Family History Race & Ethnicity More Common in black & Asians Pregnancy by ovum donation Age &Parity Teenage pregnancy <18 yrs Age>35 yrs Long interval between pregnancy >10 years Nulliparity Partner Factors Change of partner Limited sperm exposure Pregnancy by donor insemination Partner fathered an eclamptic pregnancy

14. Pregnancy Factors Multiple pregnancy Hydatiform mole Hydrops fetalis Fetal chromosomal anomaly (trisomy 13) Underlying Medical Diseae Chronic hypertension Diabetes mellitus Renal Disease Cardiovascular disease Hyperthyroidism Metabolic Syndrome Others Obesity BMI> 35 kg/m 2 Psychological stress & strain Smoking Previous history of preeclamsia

15. MILD PREECLAMPSIA GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION (≥ 140/90) Proteinuria (≥300mg /24 hr)

16. PATHO - PYSIOLOGY SYMPTOMS EXAMINATION NONE NONE Diffuse Vasospasm Capillary injury

17. LABORATORY FINDINGS MANAGEMENT Proteinuria (1- 2+) Hemoconcentration < 36 wks Conservative >36 wks MgSO4 and Delivery

18. GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION (≥ 140/90 ) NO PROTEINURIA GESTATIONAL HYPERTENSION GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION ( ≥ 140/90) Proteinuria ( ≥ 300mg /24 hr) MILD PREECLAMPSIA

19. BLOOD PRESSURE PROTEINURIA SYMPTOMS ≥ 160/110 ≥ 5grams Headache Epigastric pain Visual changes

20. LABORATORY FINDINGS SIGNS DIC Elevated Liver enzymes Pulmonary edema Oliguria cyanosis

21. new onset of seizures or unexplained coma during pregnancy in patients with pre-existing preeclampsia and without pre-existing neurological disorder.

22. addition of convulsions in a woman with preeclampsia occurs in 0.5- 4% of deliveries 25% have eclamptic seizures before labour, 50% during labour, and 25% after delivery. Eclampsia Preeclampsia Seizure/ Convulsion/ Coma

23. RISK FACTORS PATHO - PYSIOLOGY SYMPTOMS Same as P r e r e e c b l r a a m p s i a Cerebral vasospasm , ischemia and edema Generalized tonic-clonic SEIZURES ECLAMPSIA

24. LABORATORY FINDINGS MANAGEMENT Proteinuria Hemoconcentration DIC Elevated Liver enzymes Stop convulsions with MgSO4 Prompt delivery at any gestational age Lower diastolic BP 90-100mm/Hg ECLAMPSIA

25. MANAGEMENT IV MgSO4 – To prevent convulsions ( continue 24 hrs post-partum ) LOWER B.P ( hydralazine or labetalol) INDUCE LABOR (IV oxytocin and amniotomy )

26. Blood pressure ≥ 140/90 before 20 weeks of gestation. OR persistence of hypertension beyond 12 weeks after delivery .

27. CHRONIC HYPERTENSION GESTATION < 20 WEEKS OR Prepragnancy SUSTAINED HYPERTENSION (≥140/90) +/- PROTEINURIA

28. GOOD PROGNOSIS POOR PROGNOSIS WORST PROGNOSIS B.P 140/90 to 179/109 No end organ damage KIDNEYS: Renal disease EYES : Retinopathy HEART : Left Ventricular Hypertrophy (B.P >180/110) Uncontrolled HTN Chronic HTN +Superimposed PIH

29. MANAGEMENT OF CHRONIC HYPERTENSION If antihypertensive meds needed - Methyl dopa is drug of choice (or labetalol) Serial ultrasounds (increase risk of IUGR >30 weeks ) Induce labor at term DC antihypertensive meds (if B.P >100 mm Hg diastolic) Serial B.P and urine protein (watch for superimposed preeclampsia)

30. New- onset proteinuria > 300 mg/24 hrs in hypertensive women but no proteinuria before 20 wks gestation. A sudden increase in proteinuria or blood pressure or platelet count < 100,000/ cu mm in women with hypertension and proteinuria before 20 wks gestation.

31. CHRONIC HTN SUPERIMPOSED PIH CHRONIC H YPERTENSION Worsening BLOOD PRESSURE Worsening proteinuria

32. MANAGEMENT of Chronic HTN and superimposed PIH MgSO4 – To prevent convulsions ( continue 24 hrs post-partum ) LOWER B.P - Diastolic 90- 100 mm Hg ( hydralazine or labetalol) INDUCE LABOR (IV oxytocin and amniotomy )

33. HTN patients with hemolysis (H), elevated liver enzymes (EL), low platelet count (LP) 4-12% of pt. with severe preeclampsia and eclampsia develop HELLP syndrome

34. cardiovascular stabilization, correction of coagulation abnormalities, and delivery PLT transfusion before or after delivery if PLT count is <20,000/mm 3 (advised at <50,000/mm 3 before cesarean) <32 weeks gestation; steroid therapy may help stabilize maternal PLT count

35. Complex disease Appears to be triggered by the placenta Can occur in molar pregnancies where fetus absent Can also occur in abdominal pregnancy (pregnancy not in uterus )

36. Stage 3-8 weeks Stage 1 8-18 weeks Stage 2 20 weeks to birth Poor Immunoregulation Inadequate tolerance to feto- paternal antigens during conception and implantation Poor Placentation Deficient trophoblast invasion and spiral artery remodelling Clinical manifestation Over activation of maternal endothelium and systemic inflammatory network Oxidative Stress Endoplasmic reticulum Stress Inflammatory Stress

37. invasive cytotrophoblasts of fetal origin invade the maternal spiral arteries transforms them from small- caliber resistance vessels to high-caliber capacitance vessels capable of providing placental perfusion adequate to sustain the growing fetus Normal Pregnancy

38. cytotrophoblasts fail to adopt an invasive endothelial phenotype invasion of the spiral arteries is shallow and they remain small caliber, resistance vessels placental ischemia Preeclampsia

39. Defective implantation, poor Placentation Successful implantation, but failed Placentation Complete implantation failure Infertility Miscarriage Pre-eclampsia

40. Stage 1: reduced placental perfusion Abnormal implantation Stage 2 : maternal syndrome - hypertension - proteinuria - endothelial dysfunction

41. NORMAL PREGNANCY PREECLAMPSIA

42. t II

43. Impair/ inadequate trophoblast invasion to the spiral arteries Spiral arteries retain their charecteristic (narrow, tortuous, high resistance) Reduce blood supply to placenta Result in placental hypoperfusion As a compensation High BP in maternal

44. Stage 1: reduced placental perfusion Abnormal implantation Stage 2 : maternal syndrome - hypertension - proteinuria - endothelial dysfunction WHAT GETS INTO MATERNAL CIRCULATION ???

45. ANTI- ANGIOGENIC FACTORS ANGIOGENIC FACTORS Vascular endothelial growth (VEGF) including placental growth factor Transforming growth factor- beta (TGF- B) Look after maternal endothelium Soluble endoglin (sEng) Soluble FMS- like tyrosine kinase-1 (sFlt- 1) Released from diseased placenta

46. 1. vasodialator & vasoconstrictor. 2 . angiogenic and antiangiogenic factors.

47. Fetal Syndrome Maternal Syndrome 7

48. Inadequate trophoblast invasion and defect remodeling of spiral arteries Placental ischemia and inflammation Systemic inflammation Apoptosis Oxidative stress Relase of placental factor Pre-eclampsia Endothelial dysfunction 48

49. vasodialator NO vasoconstrictor Angiotensin- II Endothelin- I PGI- 2 Thromboxane A 2 placenta Syncytiotrophoblast & endothelium

50. VEGF 4\ Anf co gu l a t d V Odil tory ctors I , ,, P I GF J I ◊ y - 1 V s Bio d v eal hy e do t elial cell Blood ve . I rocoa l a a d v oco tricting f ctor pi p l C t a

51. ↓PGI2 ↑TXA2 Vasoconstriction Platelet aggregation ↑Vasopressor response ↑uterine activity

52. Activated endothelial cells promote coagulation and increase vasopressor sensitivity Widespread coagulation occur (DIC) Fibrin deposition in kidney & placenta HPT & placental insufficiency

53. Cardiovascular Generalized vasospasm Increased peripheral resistance Reduced central venous/ pulmonary pressure Hematological Platelet activation and depletion Coagulopathy Decreased plasma volume Increased blood viscosity Proteinuria Decreased glomerular filtration rate Decreased urate excretion Renal Hepatic Periportal necrosis Subscapular hematoma Cerebral oedema Cerebral haemorrhages Central Nervous System Organ Specific Changes associated with Pre- eclampsia

54. Organ Damage utero-placenta IUGR Hematological Epistaxis, DIC like features, hemoconcentration CNS Cerebral edema, cerebral hge  seizures Heart Subendothelial hge , focal necrosis & hge, cardiomyopathy, heart failure Lungs Pulmonary edema, hemorrhagic brochopneumonia Kidneys glomerular endotheliosis, oliguria liver Subcapsular hge, ischaemia  periportal necrosis, HELLP

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56. Antihypertensive drugs used in pregnancy are Methyldopa Hydralazine labetalol

57. Routinely used in severe PE. Magnesium sulphate: most commonly used. Initiated with onset of labor till 24h postpsrtum . For caesarean, started 2hrs before the section till 12hrs postpartum .

58. it can be given either IV or IM. IV has good prognosis. Loading dose for IV is 4g. i.e. 8 ml diluted in 12ml normal saline. This 20 ml is given in 20 minutes. Maintenance dose is 20 g i.e. 40ml diluted in 60ml normal saline and given at rate of 1g/hr.

59. IM is also used. Loading dose is as IV. Maintenance dose is 5g every 4 hrs in alternate buttocks for 24hrs. Mgso4 acts on NM junction and inhibit entry of Ca++ ions thus inhibiting excitability of neurons.

60. Maternal : flushing perspiration headache, muscle weakness pulmonary oedema Neonatal : lethargy hypotonia respiratory depression

61. Management of MgSO4 Toxicity

62. The only definitive treatment Preeclamptic patients divided into 3 categories A- Preeclampsia features fully subside B- partial control , but BP maintains a steady high level C- persistently increasing BP to severe level or addition of other features

63. A: can wait till spontaneous onset of labor don’t exceed Expected Date of Delivery B: >37wk terminate without delay <37wk, expectant management at least till 34wks C: terminate irrespective of POG start seizure prophylaxis and steroids if<34wks

64. Unless contraindicated: Eclamptic women should undergo normal vaginal delivery Indications for caesarean section - Fetal distress Placental abruption Unfavourable cervix Failed induction of labour Recurrent seizures

65. Urine: 24 hour urine, Proteinuria. Kidney functions : serum creatinine, urea, creatinine clearance and uric acid. Liver functions : bilirubin, Enzymes Blood : CBC, HCt , Hemolysis and Platelet count (Thrombocytopenia). Coagulation Profile: Bleeding and clotting time

66. Convulsions and coma (eclampsia). Cerebral haemorrhage. Renal failure. Heart failure. Liver failure. Disseminated intravascular coagulation. Abruptio placentae. Residual chronic hypertension in about 1/3 of cases. Recurrent pre- eclampsia in next pregnancies.

67. Intrauterine growth retardation (IUGR). Intrauterine foetal death. Prematurity and its complications.

68. Regular Antenatal checkup: rapid gain in weight rising blood pressure edema proteinuria/deranged liver or renal profile Low dose Aspirin in High risk group: ↑PGs and↓TXA2 Calcium supplementation: no effects unless women are calcium deficient Antioxidants - Vitamin C and E Nutritional supplementation : zinc, magnesium, fish oil, low salt diet

69. meningitis encephalitis space occupying lesion electrolyte disturbance vasculitis amniotic fluid embolism Medications organ failure stroke

70. N.B: Grades of proteinuria (in g/L): Trace=0.1, 1+=0.3, 2+=1, 3+=3, 4+=10 Pregnancy induced Hypertension Gestational HTN BP ≥ 140/90mmHg No evidence of underlying cause of HTN No associated symptoms Comes to normal within 6 wks of delivery Pre- eclampsia Non Severe Severe Eclampsia PreEclamsia + Convulsion ± Coma N.B: Pre- eclampsia is principally a syndrome of signs and when symptoms appear it is usually late. Assessment of the severity of pre- eclampsia is given in the next slide .

71. is most promising, but currently, none of them is completely suitable for clinical use. (Conde- Agudelo, 2014; Kleinrouweler, 2012; Myatt, 2012a). These have value for fetal- growth restriction but not preeclampsia (ACOG, 2013a). As a result of these trials, some methods to prevent Preeclampsia have been theorized… Uterine Artery Doppler Velocimetry (abnormal flow resistance/ diastolic notch in 2 nd / 3 rd trimester)

72. In preeclamptic mother: Showing early diastolic NOTCH Decreased EDF (due to high resistance) In normal mother

73. ABNORMALITIES NONSEVERE SEVERE Blood pressure ≥140/90mmHg but <160/110mmHg ≥160/110mmHg Proteinuria ≤2+ ≥3+ Oliguria Absent <400ml/day Headache Absent Present Visual disturbances Absent Present Platelet count Normal Thrombocytopenia (<100,000/mm 3 ) HELLP syndrome Absent May be present ALT,AST >70 IU/L LDH>600 IU/L Bilirubin >1.2g/L Serum transaminases (AST,ALT) Normal (<40 IU/L) Elevated Serum Creatinine Normal Elevated Epigastric pain Absent Present Fetal growth restriction Absent Obvious

74. Pre- eclampsia is a pregnancy specific disorder . It can occur in absence of the fetus. The disease is cured by the removal of the placenta .

75. Genetic Modulators Pre- existing Vascular Pathology Cytokines Ros Central players

76. 1. Maternal evaluation Hemoglobin and hematocrit platelet count : decreased, if < 1 lakh coagulation profile LFTs : indicated in all patients RFTs : raised (S.urea creatinine is decreased in Normal pregnancy) Urine Routine : proteinuria OBSTETRIC MANAGEMENT

77. 2. Fetal evaluation: Daily fetal movement count Ultrasound Doppler ultrasound for fetal blood flow

78. Genetic factor Immunologic factor Endocrinologic factor Nutritional factor Infectious factor

79. Serious hypertension BP ≥ 160/110mmHg for at least 12h Protein in the urine is over 5g/24h or +++~++++ Creatinine level increases Function of liver impaired obviously Function of the placenta impaired Fetus IUGR, asphyxia and even death

80. Gestational HTN Transient HTN of pregnancy Preeclampsia Mild Severe Eclampsia Chronic HTN preceding pregnancy Chronic HTN with superimposed pregnancy- induced hypertension Superimposed preeclampsia Superimposed eclampsia Classification of the American College of Obstetricians and Gynecologists

81. Endothelial Dysfunction/Oxidant Stress Feto- Placental unit Endocrine Dysfunction Placental Perfusion/ Vascular Resistance related Tests Uterine Artery Doppler Velocimetry AT- III ANP Renal Dysfuntion Misc Adapted from Conde- Agudelo and a ss o c i F a r t e e s e fetal DNA (2009)

82. NO YES Neither forced nor restricted

83. Gestational HTN : only if severe HTN Preeclampsia : If diastolic pressure≥ 100mm of Hg OR, there is proteinuria OR, there is fetal compromise . 37 completed weeks of gestation .

84. HEMOLYSIS (due to passage of RBCs through partially obstructed vessel) HEPATIC DYSFUNCTION (due to intravascular fibrin deposition & sinosoidal obst.) Decreased Liver blood flow H E s L ) L P Syndrome THROMBO- CYTOPENIA (due to platelet aggregation & diposition in the sites of endothhelial damage)

85. Protection in a railed cot Protection & s u p P p r o o t r e t c t i i n o n g o f c a a i r r w e a y d & u r i n g convulsion prevention of tongue bite Correction of hypoxia & acidosis Managed in Eclampsia room. Control of convulsion by MgSO4 (IM/IV route) Intermittent antihypertensive to control BP judiciously Limitation of I.V fluid Avoidance of diuretics & hyper osmotic agents 88 Prompt delivery of fetus to achieve cure

86. “ It is the most effective drug to control even recurrent seizures without any central nervous system depression to mother & fetus ” 89 Magnesium sulphate

87. 90 Not used to lower bp Produce intravascular volume depletion Worsen maternal hemoconcentration Use is limited to presence of pulmonary edema (FUROSEMIDE) May be used in persistent severe postpartum hypertension

88. Enviromental Genetics CVS and inflammatory changes Maternal immunological intolerance Abnormal placental implantaion

89. Total protein in 24 hours urine > 300mg Protein : Creatinine ratio in random sample > 0.1

90. New onset of hypertension after 20 weeks of gestation without proteinuria, followed by return of B.P. to normal within 12 weeks post- partum.

91. New onset of hypertension after 20 weeks of gestation along with properly documented proteinuria , followed by return of B.P. to normal within 12 weeks post- partum . Preeclamsia Gestational Hypertensio n Proteinuria

92. Generalized tonic-clonic seizure in a patient with Preeclampsia not attributed to any other cause. Eclampsia Preeclampsi a Seizure/ Convulsion / Coma

93. Hypertension before pregnancy / Diagnosed before 20 weeks of pregnancy not due to gestational trophoblastic disease. Hypertension diagnosed after 20 weeks but persistent after 12 weeks postpartum

94. New onset proteinuria in hypertensive women but no proteinuria before 20 weeks' gestation A sudden increase in proteinuria or blood pressure or platelet count < 100,000/L in women with hypertension and proteinuria before 20 weeks' gestation

95. Agent Dosage range Caution/comment L a bet a l o I Standard dose: 200- 800 mg orallyper day Should beavoided in women with cardiac in 2- 3 divided doses conduction abnormalities,systolic heart failure or Maximum dosage: 2,400 mgper day asthma. Ni fed i pine Standard dose: 30 60 mg orally per day Ensure correct form o f ni f ed i pineprescribed; (extended- release) Maximum do age: 120 mgp r day short acting nifedipine isno t recommen d edd u e to the risk of hyporenslon. ThereIsconcern for severehypotension if nifedip i ne i scont i nuedw i th intravenous magnesium. Methyldopa Standard dose: 250- 1 ooo mg o ally per Associated with hepatitis, hemolytic anemia, day in 2 - 3 divided doses depression, and sedation. Maximum dosage: 3000 mgper day *Modified from American Congress ofObstetricians andGynecologists.Chronic hypertension in Pregnancy. Pra c ticeBulletin num b er 1 2 5. Obstetrics andGynecology 2012; 119 (2 Part 1): 396- 407.

96. Primiparity Immunologic factors Previous pregnancy complicated by Preeclampsia/Eclampsia/HELLP Family history of Preeclampsia BMI Pregnancy related conditions

97. Primipaternity Sexual co- habituation Maternal infection Gestational age at delivery of 1 st Pregnancy Socioeconomic status Smoking

98. Angiogenic factor VEGF TFG- beta PlGF Antiangiogenic factor sFlt- 1 sEng

99. ​ History of Preeclampsia in previous pregnancy ​ Advanced maternal age ​ Family history of Preeclampsia ​ History of placental abruption, IUGR, fetal death ​ Obesity, BMI>35 doubles the risk ​ Hypertension ​ Diabetes ​ Thrombotic vascular diseases ​ Multiple gestation ​ Molar pregnancy ​ Smoking

100. Large placenta Prolonged pregnancy Placental hydrops Chromosomal abnormality