14-hypertension In Pregnancy

HYPERTENSIVE DISORDERS OF PREGNANCY JEHAD AL-HARMI DEPARTMENT OF OBS & GYN FACULTY OF MEDICINE /KUWAIT UNIVERSITY

LAKSHMI – 32 years old. Indian housewife. MF 8/12 – G1. GA = 30/52 – Presented with blurring of vision X 3 h – O/E BP = 210/120 mmHg – Admitted to ICU for control of BP – Suddenly she started shouting at the nurses to “turn the lights back on”

LAKSHMI – 32 years old. Indian housewife. MF 8/12 – G1. GA = 30/52 – Presented with blurring of vision X 3 h – O/E BP = 210/120 mmHg – Admitted to ICU for control of BP – Suddenly she started shouting at the nurses to “turn the lights back on” – CORTICAL BLINDNESS

FAT’HIYA – 42 year old. Egyptian teacher. MF 3 years – G5 P0+0+4+0. GA = 34/52 – Delivered by CS for HELLP syndrome 2 d ago – She went to the toilet unassisted – Found ½ h later unconscious – Laparotomy carried out for hemoperitoneum – Patient died on the table

FAT’HIYA – 42 year old. Egyptian teacher. MF 3 years – G5 P0+0+4+0. GA = 34/52 – Delivered by CS for HELLP syndrome 2 d ago – She went to the toilet unassisted – Found ½ h later unconscious – Laparotomy carried out for hemoperitoneum – Patient died on the table – RUPTURED HEPATIC HEMATOMA

MALEEHA – 38 year old. Kuwaiti secretary. MF 10 years – G5 P2+2+0+4. GA = 38/52. No ANC – Morbidly obese, diabetic & hypertensive – Presented with loss of FM X 2 d & heavy vaginal bleeding X 2 h. BP = 200/100 mmHg – Delivered in RR; macerated SB. BW= 1000g – She had a fit immediately after delivery; she was rushed to ICU. Cardiac arrest 10 minutes later

MALEEHA – 38 year old. Kuwaiti secretary. MF 10 years – G5 P2+2+0+4. GA = 38/52. No ANC – Morbidly obese, diabetic & hypertensive – Presented with loss of FM X 2 d & heavy vaginal bleeding X 2 h. BP = 200/100 mmHg – Delivered in RR; macerated SB. BW= 1000g – She had a fit immediately after delivery; she was rushed to ICU. Cardiac arrest 10 minutes later – ECLAMPSIC FIT

INTRODUCTION • Pre-eclampsia (PE) complicates 7% of all pregnancies • Second to pulmonary embolism as a cause of maternal mortality; responsible for 15% of all maternal deaths • Important cause of perinatal morbidity & mortality due to direct fetal effects & iatrogenic preterm delivery for maternal sake

TERMINOLOGY - 1 • Many classifications • National High Blood Pressure Education Program Working Group revised the classification system in 2000 • Adopted by ACOG • 4 categories are recognized

TERMINOLOGY - 2 1. 2. 3. 4.

CHRONIC HYPERTENSION PE GESTATIONAL HYPERTENSION CHRONIC HYPERTENSION WITH SUPERIMPOSED PE

TERMINOLOGY - 3 • Chronic hypertension: – Predates the pregnancy – Identified before 20/52 gestation – Exceptions: • • • •

GTD Fetal triploidy Hydrops fetalis Drugs (eg, cocaine)

– Persists > 12/52 postpartum

TERMINOLOGY - 4 • PE: – PE is a multi-organ disease process affecting • • • •

Kidneys CNS Liver Hematological system

– Hypertension and proteinuria – Absolute rather than relative definition for BP – 24-hour urine collection or dipstick

TERMINOLOGY - 5 • Gestational hypertension: – High BP after 20/52 pregnancy without proteinuria – Previously termed pregnancy-induced hypertension (PIH)

• Chronic hypertension with superimposed PE: – Increased BP and proteinuria in a woman known to have chronic hypertension

EPIDEMIOLOGY - 1 WHAT ARE THE RISK FACTORS FOR PE?

EPIDEMIOLOGY - 2 WHAT ARE THE RISK FACTORS FOR PE? – Chronic renal disease (20X) – Antiphospholipid syndrome (10X) – Chronic hypertension (10X) – Nulliparity (3X) : incidence in primigravidas is 14-22% compared with 6-7% in multiparous women – Extremes of age: < 15 or > 35 years (3X for latter)

EPIDEMIOLOGY - 3 WHAT ARE THE RISK FACTORS FOR PE? – Family history of PET in a 1st degree relative (5X) – Multiple pregnancy (4X) – DM (2X) – Black race – Sickle cell disease – Hydrops fetalis, mirror syndrome – Altered paternity

EPIDEMIOLOGY - 4 • Recurrence rate of PE: – For primigravidas 25% 50% – For multiparas – Affected by: • GA at onset of PE in the index pregnancy • Severity • Presence of underlying maternal disease

• No increased risk for chronic hypertension in the future except in the cases of recurrent PE

CLINICAL FEATURES - 1 • HYPERTENSION: – Increase in BP to 140 mm Hg systolic or 90 mm Hg diastolic – Sustained (at least 2 readings 6 hours apart within the same week) – Ideal measurement in sitting or lateral decubitus position (upper arm) – Which is better for diastolic BP IV or V Korotcoff sound? Why?

CLINICAL FEATURES - 2 • Classically PE used to be defined as a triad of hypertension, dependent edema, and proteinuria • But nowadays edema is no longer required to make the diagnosis • Why?

CLASSIFICATION - 1 • MILD OR SEVERE • NO MODERATE CATEGORY IN PE • Criteria for severity: – BP>160 mm Hg systolic or 110 mm Hg diastolic – Proteinuria > 5 g/24 hour (normal < 300 mg). How does this correlate with the dipstick values? – Elevated serum creatinine – Grand-mal seizures (eclampsia)

CLASSIFICATION - 2 • Criteria for severity: – Pulmonary edema – Oliguria (urine output < 500 cc/24 hour) – Microangiopathic hemolysis – Thrombocytopenia (platelets < 100) – Hepatocellular damage (elevated ALT & AST) – IUGR or IUFD – Oligohydramnios (AFI < 5 cm) – Headache, visual disturbances, epigastric or RUQ pain

ETIOLOGY - 1 UNKNOWN 1. IMMUNE RESPONSE: – Inadequate maternal antibody production to fetal allograft resulting in vascular damage from circulating immune complexes – This is supported by evidence from cases with: • •

Limited prior antigen exposure (young nulliparous women, altered paternity) Increased fetal antigens (large placenta in twins, molar pregnancy, hydrops fetalis, & DM)

ETIOLOGY - 2 2. CIRCULATING TOXINS: 3. VASOACTIVE SUBSTANCES: – Vasoactive substances found in maternal blood, amniotic fluid, & placenta (eg, nitric oxide deficiency) – Increased sensitivity to vasopressin, epinephrine & norepinephrine – Loss of third trimester resistance to angiotensin II

ETIOLOGY - 3 4. ENDOTHELIAL DAMAGE: – Primary endothelial damage (cause unknown) leads to decreased prostacyclin (vasodilator) & increased thromboxane A2 (vasoconstrictor) – Low-dose aspirin or heparin may play a role in prevention

5. DIETARY DEFICIENCY: – Ca supplementation reduces the incidence of PE in some populations

ETIOLOGY - 4 6. PRIMARY DIC: – Thrombi formation & deposition leads to vessel damage especially in the kidneys & placenta

7. ABNORMAL TROPHOBLAST INVASION: – 2nd wave of trophoblast invasion at 16/52 – Trophoblasts normally invade muscular layer in walls of spiral arterioles

PATHOPHYSIOLOGY - 1 CARDIOVASCULAR ASPECTS: – Increased BP due to increased systemic vascular resistance & cardiac output – Arteriolar vasospasm causes most of the serious end organ effects – Loss of blunted pressor response to angiotensin II

PATHOPHYSIOLOGY - 2 CARDIOVASCULAR ASCEPTS: – Increased afterload & decreased ventricular preload – Reduction in the synthesis of prostacyclin relative to thromboxane A2 leads to arteriolar vasospasm – Alteration in the synthesis of endothelium derived relaxing agent (endothelin-I) & nitric oxide

PATHOPHYSIOLOGY - 3 HEMATOLOGICAL ASPECTS: – Plasma volume contraction leading to reduced regional perfusion & increased risk of hypovolemic shock in case of hemorrhage – Clinically  increased hematocrit (hemoconcentration) – This is in spite of increased total body water & sodium

PATHOPHYSIOLOGY - 4 HEMATOLOGICAL ASPECTS: – Arteriolar spasm leads to microangopathic hemolysis which manifests itself initially as thrombocytopenia – HELLP syndrome (Hemolysis, Elevated Liver enzymes, &/or Low Platelets)

PATHOPHYSIOLOGY - 5 RENAL ASPECTS: – Reduced glomelular filtration rate (GFR), proteinuria, & Na retention – Reduced GFR due to reduced renal plasma flow & reduced filtration fraction (GFR/RPF) – Reduced clearance of uric acid often seen; reflected as hyperuricemia. This precedes fall of GFR – Glomelular damage leads to leakage of protein

PATHOPHYSIOLOGY - 6 NEUOROLOGICAL ASPECTS: – Hyperreflexia does not correlate with disease severity – Generalized tonic-clonic seizures: • • • •

Occur in 1 in 1,000 deliveries or 1% of PE patients Seen in many cases that end in maternal death May occur up to 24 hours after delivery Cause unknown

PATHPHYSIOLOGY - 7 NEUOROLOGICAL ASPECTS: – Headache & visual disturbances (blurred vision & scotomata) occur due to retinal artery spasm – Retinal hemorrhage may be seen in severe cases – Retinal detachment occurs rarely – Blindness may be peripheral or central

PATHOPHYSIOLOGY - 8 PULMONARY EDEMA: – Due to decreased colloid oncotic pressure, pulmonary capillary leakage, LVF, iatrogenic fluid overload, or a combination of the above

HEPATOCELLULAR DAMAGE: – Due to vasospasm & ischemia. Result in focal peripheral hemorrhage, infarction, or rupture

PATHOPHYSIOLOGY - 9 FLUID & ELECTROLYTE BALANCE: – Increased extravascular volume seen as increased weight &/or dependant edema – Decreased bicarbonate level due to lactic acidosis with compensatory metabolic alkalosis; especially after eclamptic fits – Increased ADH & atrial natriuretic factor

FETAL COMPLICATIONS 1. 2. 3. 4. 5. 6.

IUGR Oligohydramnios Placental abruption &/or infarction Consequences of prematurity FD due to utero-placental insufficiency Increased perinatal morbidity & mortality

MATERNAL COMPLICATIONS 1. 2. 3. 4. 5. 6. 7.

CNS manifestations: seizures & stroke DIC Increased likelihood of CS Pulmonary edema ARF Hepatic failure or rupture Maternal mortality

TREATMENT - 1 DELIVERY IS THE ONLY DEFINITIVE TREATMENT: – Generally indicated for women near term with PE of any degree & for women with severe disease at any gestational age – Use of corticosteroids is appropriate before 34/52 in some cases

TREATMENT - 2 • Some manifestations of severe PE (oliguria, renal failure, HELLP syndrome) mandate expedient delivery regardless of gestational age • For preterm women with mild PE, conservative management is generally indicated with close monitoring (BP, proteinuria, LFT/RFT, CBC, U/S, NST, BPP)

TREATMENT - 3 MgSO4 is used for seizure prophylaxis in severe PE: – Mechanism of action – IV loading dose of 4 g over 20 minutes followed by continuos infusion at 2-3 g/h – Stop MgSO4 if any of the following occur: • • •

Loss of deep tendon reflexes RR <12/min Urine output < 25 cc/h

TREATMENT - 4 – Therapeutic range = 2-3 mmol/l – Antidote = 1 g Ca gluconate (10 cc of 10%) given iv over 2 minutes – Contraindications

TREATMENT - 5 Control of maternal BP during labor using antihypertensive drugs: – Indicated if systolic BP>170 mm Hg or diastolic BP>110 mm Hg – Loss of autoregulation may predispose to the development of strokes

TREATMENT - 6 • Hydralazine: – 5-10 mg boluses repeated every 20 min SOS – May be given continuously – Causes tachycardia

• Labetalol: – 20 mg iv every 10 min; maximum of 300 mg – Or continuous infusion with BP monitoring

TREATMENT - 7 • Verapamil: – 10 mg S/L repeated after 30 min

• Na nitroprusside: – Last resort

TREATMENT - 8

DELIVERY: – Vaginal route preferable over CS even in patients with severe disease – Cervical ripening with PGE2 or Foley catheter can be considered

TREATMENT - 9 ANESTHESIA: – For labor & delivery: • Parenteral analgesia. Pethidine! • Epidural block. But beware of hypotension & thrombocytopenia

– For CS: • GA associated with elevation of BP during induction & reversal • Epidural block

PREVENTION 1. LOW-DOSE ASPIRIN: 60-80 mg OD. May be appropriate for women at high risk for developing PE. Not recommended for prophylaxis in unselected, normotensive patients 1. REDUCED NA INTAKE 2. CA SUPPLEMENTATION: 2 g Ca gluconate OD. 3X reduction in PE in angiotensin-sensitive women

CHRONIC HYPERTENSION - 1 Mild-moderate chronic hypertension: – Systolic BP= 140-180 mmHg, diastolic BP= 90-100 mmHg – Unlikely to have any significant deleterious maternal effects – May have serious detrimental effects on the fetus such as IUGR, placental abruption & IUFD – No apparent benefits to treatment

CHRONIC HYPERTENSION - 2 Severe hypertension: – Systolic BP > 180 mmHg, diastolic BP> 100 mmHg – May require antihypertensive therapy to prevent maternal morbidity & mortality

CHRONIC HYPERTENSION - 3 • Patients already on medication may continue therapy (even in second trimester) • If therapy is to be initiated during pregnancy, the first line agent is alpha-methyl dopa (250 mg X 3 - 500 mg X 4) • Beta-blockers (labetalol 100 mg X 2- 300 mg X 4 or atenolol 50-100 mg X 1). Beware of IUGR

CHRONIC HYPERTENSION - 4 • ACE inhibitors are contraindicated because they may lead to fetal anomalies, renal failure & oligohydramnios, IUFD & NND • Diuretics should not be started during pregnancy. The reduced plasma volume may have adverse fetal effects. Used as last resort only

CHRONIC HYPERTENSION - 5

• Increased risk of IUGR. Serial U/S & NST to monitor fetal well-being • Significant risk for superimposed PE. Monitor BP & proteinuria; & deliver at term

OTHERS • Management of: – Gestational hypertension: • Less likelihood of complications • Less need for intervention

– Chronic hypertension with superimposed PE: • Similar to management of PE arising de novo during pregnancy • Role of prophylaxis

CONTRACEPTION • Patients with PE can use the combined oral contraceptive pill (OCP) 2/52 after delivery if BP has returned to normal • Women with well-controlled & monitored hypertension < 35 years old may try OCP (< 35 mg ethinyl estradiol) if otherwise healthy & without end-organ vascular disease • ALTERNATIVES

CASE - 1 MARIUM – 19 year old. MF 9/12 – G1. GA = 35/52 – C/O headache & epigastric pain X 1 day – BP = 180/120 mm Hg – Proteinuria 4 + – OUTLINE MANAGEMENT

CASE - 2 AMEENA – 36 year old. MF 9 years – G7 P2+1+3+2. GA = 30/52 – Previous CS at 28/52 for severe PE. BW 500 g. NND after 2/7 – Routine ANC visit, BP = 150/90 mm Hg – OUTLINE MANAGEMENT

CASE - 3 HESSA – 40 year old. MF 15 years – G7 P6+0+0+6. All FTND. GA = 12/52 – C/O vaginal bleeding X 2/7 – O/E BP = 160/100 mm Hg. Proteinuria 2+ – P/V uterus = 16/52. Os closed – DISCUSS DIFFRENTIAL DIAGNOSIS & MANAGEMENT

CASE - 4 FATMA – 32 year old. MF 1 year – G1. GA = 30/52 – Routine ANC visit – BP = 150/95 mm Hg – Proteinuria 1+ – DISCUSS FURTHER MANAGEMENT

CASE - 5 AYSHA – 38 year old. MF 12 years – G6 P4+0+1+4. All FTND. GA = 12/52 – First ANC. BP = 160/105 mm Hg – OUTLINEM MANAGEMENT

THE END